Bilateral Lateral Prefrontal Cortex Research Articles

Amygdala resting-state functional connectivity alterations in patients with chronic insomnia disorder: correlation with electroencephalography beta power during sleep.

This study investigated alterations in resting-state functional connectivity (RSFC) and hyperarousal biomarkers in patients with chronic insomnia disorder (CID), compared with good sleepers (GS). We also examined the relationships between altered RSFC and hyperarousal biomarkers. Fifty patients with CID and 52 GS completed self-reporting questionnaires, and then underwent polysomnography and resting-state functional magnetic resonance imaging. We analyzed RSFC in the amygdala (AMG) and anterior insula (aINS), which are core regions of the salience network that are likely to be involved in hyperarousal. We also analyzed electroencephalography (EEG) relative beta power and heart rate variability (HRV) parameters (e.g. low and high frequency) during sleep. We then tested between-group differences in the RSFC and hyperarousal biomarkers; we examined correlations of RSFC with EEG beta power and HRV. Compared with GS, patients with CID showed more negative RSFC between the right amygdala (R.AMG) and left supramarginal gyrus (L.SMG), but less positive RSFC between the left aINS and bilateral lateral prefrontal cortex. The R.AMG-L.SMG RSFC was negatively correlated with EEG beta power in central regions (C3: r = -0.336, p = 0.012; C4: r = -0.314, p = 0.024). Decreased RSFC between the R.AMG and L.SMG in patients with insomnia may reflect the difficulty in cortical top-down regulation of the AMG, indicating daytime hyperarousal. Individuals who experience hyperarousal during the daytime may also exhibit cortical hyperarousal during sleep, as indicated by increased EEG beta power.

0383 Amygdala Resting State Functional Connectivity Change Correlates with Sleep EEG Beta Power in Chronic Insomnia Disorder Patients

Abstract Introduction Physiological hyperarousal is suggested as a core feature of insomnia and resting-state functional magnetic resonance imaging (rs-fMRI) studies have examined the neurobiological basis of the hyperarousal theory. However, few have investigated the associations between rs-fMRI and the biomarkers of physiological hyperarousal. We aimed to investigate (1) the differences in the resting-state functional connectivity (RSFC) between chronic insomnia disorder (CID) patients and good sleepers (GS), and (2) the relationships between altered RSFC and the hyperarousal biomarkers including electroencephalogram (EEG) and heart rate variability (HRV). Methods Fifty CID patients (37 females, 45.8±12.7 years old) and 52 GS (32 females, 37.0±13.2 years old) completed self-report questionnaires, and underwent nocturnal polysomnography and rs-fMRI. We analyzed RSFC in the amygdala (AMYG) and anterior insula (AI), which were core regions of the salience network probably associated with hyperarousal. We also analyzed EEG relative beta power at central derivations and frequency domain HRV parameters (e.g., low frequency and high frequency) in ECG lead ll during sleep. We then tested differences in the RSFC between CID and GS and examined the correlations between RSFC, EEG beta power, and HRV. Results Compared with GS, CID showed more negative RSFC between the right AMYG and left supramarginal gyrus (SMG), but less positive RSFC between the left AI and bilateral lateral prefrontal cortex (LPFC). The right AMYG-left SMG RSFC was positively correlated with EEG beta power in non-rapid eye movement (NREM) stage 3 sleep measured on central regions (C3: r=-0.336, p=0.012; C4: r=-0.314, p=0.024). We did not find any significant correlations between RSFC and HRV parameters. Conclusion Decreased RSFC between the AMYG and SMG in insomnia patients may reflect a difficulty in the cortical top-down regulation of the amygdala, indicating hyperarousal during daytime. We also found a significant correlation between the AMYG-SMG RSFC and EEG beta power. This result suggests that altered AMYG connectivity during daytime is associated with cortical hyperarousal during sleep. Overall, our study may provide neurobiological evidence for the 24-hour hyperarousal theory of insomnia. Support (if any) The Korea Institute for Advancement of Technology funded by the Ministry of Trade, Industry and Energy (study no.: P0014279, 20009210).

Prefrontal activation and pupil dilation during n-back task performance: A combined fNIRS and pupillometry study

The n-back task is one of the most commonly used working memory (WM) paradigms in cognitive neuroscience. Converging evidence suggests activation in the lateral prefrontal cortex (PFC) and pupil dilation [a proxy for locus coeruleus (LC) activation] during this task. However, it remains unclear whether the lateral PFC and the LC are functionally associated during n-back task performance. This study's aim was to examine the relationship between changes in lateral PFC activity and the pupil diameter and to evaluate the effect of WM load on such relationship during the n-back task. Thirty-nine healthy young adults (10 males, 29 females) underwent a number n-back paradigm with 0- and 3-back conditions. Their prefrontal hemodynamics and changes in pupil size during task performance were simultaneously measured using a 16-channel functional near-infrared spectroscopy (fNIRS) device and a wearable eye tracker. Young adults exhibited significant activation in the bilateral lateral PFC and significant increases in pupil size when the WM load was high (i.e., 3-back) but not low (i.e., 0-back) compared with the resting period. Interestingly, significant positive correlations were found between changes in lateral PFC activity and pupil size during the 0-back task only. These correlations tended to be stronger during the 0-back than the 3-back condition. Thus, the functional relationship between the lateral PFC and the LC may vary at different load levels during the n-back task. Our findings have important implications for neuropsychiatric research and support concurrent fNIRS and pupillometric measurements for a better understanding of the mechanisms underlying WM processing.

Negative Learning Bias in Depression Revisited: Enhanced Neural Response to Surprising Reward Across Psychiatric Disorders

BackgroundPrior work has proposed that major depressive disorder (MDD) is associated with a specific cognitive bias: patients with depression seem to learn more from punishment than from reward. This learning bias has been associated with blunting of reward-related neural responses in the striatum. A key question is whether negative learning bias is also present in patients with MDD and comorbid disorders and whether this bias is specific to depression or shared across disorders. MethodsWe employed a transdiagnostic approach assessing a heterogeneous group of (nonpsychotic) psychiatric patients from the MIND-Set (Measuring Integrated Novel Dimensions in Neurodevelopmental and Stress-Related Mental Disorders) cohort with and without MDD but also with anxiety, attention-deficit/hyperactivity disorder, and/or autism (n = 66) and healthy control subjects (n = 24). To investigate reward and punishment learning, we employed a deterministic reversal learning task with functional magnetic resonance imaging. ResultsIn contrast to previous studies, patients with MDD did not exhibit impaired reward learning or reduced reward-related neural activity anywhere in the brain. Interestingly, we observed consistently increased neural responses in the bilateral lateral prefrontal cortex of patients when they received a surprising reward. This increase was not specific to MDD, but generalized to anxiety, attention-deficit/hyperactivity disorder, and autism. Critically, increased prefrontal activity to surprising reward scaled with transdiagnostic symptom severity, particularly that associated with concentration and attention, as well as the number of diagnoses; patients with more comorbidities showed a stronger prefrontal response to surprising reward. ConclusionsPrefrontal enhancement may reflect compensatory working memory recruitment, possibly to counteract the inability to swiftly update reward expectations. This neural mechanism may provide a candidate transdiagnostic index of psychiatric severity.

Study on brain glucose metabolic networks in Parkinson’s disease patients with visual spatial dysfunction by 18F-FDG PET imaging

Aim: To assess the changes of brain glucose metabolism and abnormal intracerebral loop in early Parkinson’s disease (PD) patients with visual spatial dysfunction by [Formula: see text]F-fluorodeoxyglucose ([Formula: see text]F-FDG) positron emission tomography (PET) imaging. Materials and Methods: This study includes three groups: early PD patients with visual spatial dysfunction ([Formula: see text]), early PD patients without visual spatial dysfunction ([Formula: see text]) and healthy controls ([Formula: see text]). Resting-state [Formula: see text]F-FDG PET was performed to obtain the imaging of brain glucose metabolism. Statistical Parametric Mapping (SPM) was used for data analyses to compare the brain glucose metabolic changes among different groups. Results: Compared with the healthy controls, early PD patients (with/without visual spatial dysfunction) showed hypermetabolism in putamen, globus pallidus, thalamus, pons, cerebellum and primary motor cortex, and hypometabolism in part of the occipital and temporal lobes. Compared with early PD patients without visual spatial dysfunction, those with visual spatial dysfunction further showed hypometabolism in visual regions including bilateral lateral prefrontal cortices and posterior parietal lobules, besides occipital and temporal lobes. Conclusion: The occurrence of abnormal glucose metabolism in the brain visual processing areas was closely associated with visual spatial dysfunction in PD patients.

Changes in Resting-State Cerebral Activity in Patients with Hyperthyroidism: A Short-Term Follow-Up Functional MR Imaging Study

To investigate the brain functional abnormality of hyperthyroid patients before and after treatment for one month using resting-state functional magnetic resonance imaging (rs-fMRI). Amplitude of low-frequency fluctuation (ALFF) and seed-based functional connectivity (FC) analysis were performed in 27 new-onset untreated hyperthyroid patients relative to 30 healthy controls. In addition, follow-up data were available for 19 patients treated with methimazole for one month. Compared with healthy controls, patients exhibited lower ALFF in the right posterior cingulate cortex (PCC); increased FC in the bilateral anterior insula (AI), bilateral posterior insula (PI) and left anterior lobe of the cerebellum (ALC); and decreased FC in the bilateral lateral prefrontal cortex (LPFC), the right medial temporal gyrus (MTG) and the bilateral PCC. Compared with the hyperthyroid status, patients with improved thyroid function showed increased FC in the right LPFC and right dorsolateral prefrontal cortex (DLPFC). Subsequently, Pearson’s correlation analyses were performed between abnormal ALFF, FC, neuropsychological assessment and serum free triiodothyronine (FT3) levels. The results indicated that the alterations in regional and network-level brain functions, which might underlie different psychiatric complications were dynamic and interactional processes in hyperthyroidism. Moreover, the improvement in regional brain FC was correlated with the efficacy of anti-thyroid medication.

Left Lateral Prefrontal Activity Reflects a Change of Behavioral Tactics to Cope with a Given Rule: An fNIRS Study.

Rules prescribe human behavior and our attempts to choose appropriate behavior under a given rule. Cognitive control, a mechanism to choose and evaluate actions under a rule, is required to determine the appropriate behavior within the limitations of that rule. Consequently, such cognitive control increases mental workload. However, the workload caused by a cognitive task might be different when an additional rule must be considered in choosing the action. The present study was a functional near-infrared spectroscopy (fNIRS) investigation of an experimental task, in which the difficulty of an operation and existence of an additional rule were manipulated to dissociate the influence of that additional rule on cognitive processing. Twenty healthy Japanese volunteers participated. The participants performed an experimental task, in which the player caught one of five colored balls from the upper part of a computer screen by operating a mouse. Four task conditions were prepared to manipulate the task difficulty, which was defined in terms of operational difficulty. In turn, operational difficulty was determined by the width of the playable space and the existence of an additional rule, which reduced the score when a red ball was not caught. The 52-channel fNIRS data were collected from the forehead. Two regions of interest (ROIs) associated with the bilateral lateral prefrontal cortices (LPFCs) were determined, and a three-way repeated-measures analysis of variance (ANOVA) was performed using the task-related signal changes from each ROI. The fNIRS results revealed that bilateral LPFCs showed large signal changes with the increase in mental workload. The ANOVA showed a significant interaction between the existence of an additional rule and the location of the ROIs; that is, the left lateral prefrontal area showed a significant increase in signal intensity when the additional rule existed, and the participant occasionally decided to avoid catching a ball to successfully catch the red-colored ball. Thus, activation of the left LPFC corresponded more closely to the increase in cognitive control underlying the behavioral change made to cope with the additional rule.

Altered frontal pole development affects self-generated spatial working memory in ADHD

BackgroundSpatial working memory (SWM) dysfunction is a feature of attention deficit hyperactivity disorder (ADHD). Previous studies suggested that behavioral performance in self-generated SWM improves through development in children with and without ADHD. Nevertheless, developmental changes in the neural underpinnings of self-generated SWM are unknown. MethodUsing near-infrared spectroscopy, hemodynamic activity in the prefrontal cortex (PFC) was measured in 30 children with ADHD (9.5±1.6years-old) and 35 TD children (9.0±1.6years-old) while they performed a self-generated SWM task. We then investigated correlations between age and behavioral performance, and between age and hemodynamic activity in the PFC for each group. ResultsBoth groups showed a negative correlation with age and number of errors [ADHD: r(28)=−0.37, p=0.040; TD: r(33)=−0.59, p<0.001], indicating that self-generated SWM improves through development. The TD group showed a positive correlation between age and oxygenated hemoglobin in the frontal pole [10ch: r(33)=0.41, p=0.013; 11ch; r(33)=0.44, p=0.008] and bilateral lateral PFC [4ch: r(33)=0.34, p=0.049; 13ch; r(33)=0.54, p=0.001], while no significant correlation was found in the ADHD group. Furthermore, regression slopes for the frontal pole significantly differed between the TD and ADHD groups [10ch: t(61)=2.35, p=0.021; 11ch: t(61)=2.05, p=0.044]. ConclusionChildren with ADHD showed abnormalities in functional maturation of the frontal pole, which plays a role in manipulating and maintaining information associated with self-generated behavior.

The neural basis of value accumulation in intertemporal choice.

Making intertemporal choices (choosing between rewards available at different points in time) requires determining and comparing the subjective values of available rewards. Several studies have found converging evidence identifying the neural systems that encode subjective value in intertemporal choice. However, the neural mechanisms responsible for the process that produces intertemporal decisions on the basis of subjective values have not been investigated. Using model-based and connectivity analyses of functional magnetic resonance imaging data, we investigated the neural mechanisms underlying the value-accumulation process by which subjective value guides intertemporal decisions. Our results show that the dorsomedial frontal cortex, bilateral posterior parietal cortex, and bilateral lateral prefrontal cortex are all involved in the accumulation of subjective value for the purpose of action selection. Our findings establish a mechanistic framework for understanding frontoparietal contributions to intertemporal choice and suggest that value-accumulation processes in the frontoparietal cortex may be a general mechanism for value-based choice.

Hyper-coupling between working memory task-evoked activations and amplitude of spontaneous fluctuations in first-episode schizophrenia

Working memory (WM) deficit is an important component of impaired cognition in schizophrenia. However, between-studies inconsistencies as to the specific functional substrate imply that inter-individual variability (IIV) in the WM performance is associated with IIV in brain activity in schizophrenia. To examine the neural substrate of this WM IIV, we studied whether the neural mechanisms that underlie individual differences in WM capacity are the same in schizophrenia patients and healthy people. We correlated the IIV of the task-evoked brain activity and task performance during an n-back WM task with the IIV of the moment-to-moment variability in intrinsic resting-state activity, as measured by the amplitude of low-frequency fluctuations (ALFFs) and further compared this relationship between 17 patients with first-episode schizophrenia (FES) and 18 healthy controls. Between-group comparisons of the correlation patterns indicated aberrant ALFF-WM activation correlations and ALFF-WM performance correlations in the FES patients, but no significant changes were detected in any single measurement of these three characteristics. Specifically, we found increased positive ALFF-WM activation correlations in the bilateral lateral prefrontal cortices, posterior parietal cortices and fusiform gyri in the FES patients. We also observed significant increases in positive ALFF-WM performance correlations in the bilateral ventromedial prefrontal cortices in the FES patients. This hyper-coupling between the ALFF and fMRI measures during a WM task may indicate that it was difficult for the patients to detach themselves from one state to transition to another and suggests that the inefficient cortical function in schizophrenia stems from the intrinsic functional architecture of the brain.

How stable is activation in the amygdala and prefrontal cortex in adolescence? A study of emotional face processing across three measurements

Prior developmental functional magnetic resonance imaging (fMRI) studies have demonstrated elevated activation patterns in the amygdala and prefrontal cortex (PFC) in response to viewing emotional faces. As adolescence is a time of substantial variability in mood and emotional responsiveness, the stability of activation patterns could be fluctuating over time. In the current study, 27 healthy adolescents (age: 12-19 years) were scanned three times over a period of six months (mean test-retest interval of three months; final samples N=27, N=22, N=18). At each session, participants performed the same emotional faces task. At first measurement the presentation of emotional faces resulted in heightened activation in bilateral amygdala, bilateral lateral PFC and visual areas including the fusiform face area. Average activation did not differ across test-sessions over time, indicating that at the group level activation patterns in this network do not vary significantly over time. However, using the Intraclass Correlation Coefficient (ICC), fMRI reliability demonstrated only fair reliability for PFC (ICC=0.41-0.59) and poor reliability for the amygdala (ICC<0.4). These findings suggest substantial variability of brain activity over time and may have implications for studies investigating the influence of treatment effects on changes in neural levels in adolescents with psychiatric disorders.

Relation between working memory performance and evoked cerebral blood oxygenation changes in the prefrontal cortex evaluated by quantitative time-resolved near-infrared spectroscopy

Objectives: The lateral prefrontal cortex (LPFC) plays a central role in working memory (WM). In the present study, we employed quantitative, near-infrared time-resolved spectroscopy (TRS) to evaluate the relation between LPFC activity during WM and the task performance in 19 healthy, middle-aged, female subjects (mean age of 46·8±2·1 years).Methods: Concentration changes of oxyhemoglobin (oxy-Hb), deoxyhemoglobin, and total hemoglobin in the bilateral LPFC were measured by means of TRS during performance of Sternberg tests (ST) of one digit and six digits. The oxy-Hb changes were compared to performance in ST. In addition, we evaluated whether pathlength of the forehead and baseline concentration of oxy-Hb influenced WM performance.Results: TRS revealed increases in oxy-Hb in association with a decrease in deoxy-Hb during ST. We found a significant negative correlation between the reaction time of six-digit ST and oxy-Hb changes in the bilateral LPFC (left, P = 0·0061; right, P = 0·0029); however, no significant correlation was observed with one-digit ST. In contrast, accuracy of ST did not correlate with the oxy-Hb changes in the prefrontal cortex. The optical pathlength of the forehead and concentration of oxy-Hb at rest in the LPFC did not correlate with either reaction time or accuracy in ST.Conclusion: The present results indicate that oxy-Hb changes in the LPFC during a WM task, as measured by TRS, correlated with WM performance. TRS is compact and less expensive than functional magnetic resonance imaging, and may be a useful tool to evaluate neural correlates of WM in normal adults.

Strength of default mode resting‐state connectivity relates to white matter integrity in children

A default mode network of brain regions is known to demonstrate coordinated activity during the resting state. While the default mode network is well characterized in adults, few investigations have focused upon its development. We scanned 9-13-year-old children with diffusion tensor imaging and resting-state functional magnetic resonance imaging. We identified resting-state networks using Independent Component Analysis and tested whether the functional connectivity between the medial prefrontal cortex (mPFC) and posterior cingulate cortex (PCC) depends upon the maturation of the underlying cingulum white matter tract. To determine the generalizability of this relationship, we also tested whether functional connectivity depends on white matter maturity between bilateral lateral prefrontal cortex (lateral PFC) within the executive control network. We found a positive relationship between mPFC-PCC connectivity and fractional anisotropy of the cingulum bundle; this positive relationship was moderated by the age of the subjects such that it was stronger in older children. By contrast, no such structure-function relationship emerged between right and left lateral PFC. However, functional and structural connectivity of this tract related positively with cognitive speed, fluency, and set-switching neuropsychological measures.

Selective Ablations Reveal That Orbital and Lateral Prefrontal Cortex Play Different Roles in Estimating Predicted Reward Value

Subregions of prefrontal cortex are important for estimating reward values and using these values to guide behavior. The present studies directly tested whether orbital prefrontal cortex (O-PFC) and lateral prefrontal cortex (L-PFC) are necessary for evaluating trial-to-trial changes in the reward values predicted by visual cues. We have compared intact rhesus monkeys, those with bilateral O-PFC lesions (n = 3), and those with bilateral L-PFC lesions (n = 3). We used three versions of a visually cued color discrimination task: we varied reward size, delay to reward, or both. O-PFC lesions altered estimations of predicted reward value in all versions of the task. L-PFC lesions disrupted performance only when both reward size and delay to reward were varied together. Neither lesion directly affected basic internal drive states (satiation curves). Our results suggest that O-PFC is essential for establishing independent, context-specific scales with which predicted reward values are measured. L-PFC appears necessary for integration of predicted reward value across these different scales.

Process-specific prefrontal contributions to episodic encoding and retrieval of tastes: A functional NIRS study

The neural basis of memory subprocesses, encoding and retrieval, have been extensively examined in functional neuroimaging studies. However, the cortical substrates of taste memory, which form an important part of our episodic memory, have rarely been explored in humans. Previously, we have used functional near-infrared spectroscopy (fNIRS) and found activation of the lateral prefrontal cortex (LPFC) related to taste encoding. The method used in the current study allowed brain monitoring while participants tasted liquid taste-stimuli in upright positions. Here, using the same system, we examined the LPFC activity of 28 healthy volunteers during both the encoding and the retrieval of taste memory. The contrast between the retrieval and eyes-closed-resting conditions revealed activation in the bilateral LPFC. This activation was significantly larger than that for encoding in the bilateral frontopolar and right dorso-LPFC regions, particularly in the right hemisphere (N=28, P<0.05, FDR corrected), exhibiting right hemispheric dominance. Our findings are in line with the hemispheric encoding/retrieval asymmetry (HERA) model, which proposes a process-specific prefrontal contribution to memory function.

Monkeys Quickly Learn and Generalize Visual Categories without Lateral Prefrontal Cortex

Categorization is a basic mental process that helps individuals distinguish among groups of negative and positive objects, e.g., poisons and nutrients, or predators and prey. Monkey experiments have suggested that lateral prefrontal cortex (LPFC) participates in learning and processing visual categories. However, in humans category specific visual agnosia follows inferior temporal cortex but not LPFC damage. Here, we use a new behavioral approach to show that both normal monkeys and those with bilateral removal of LPFC learn and generalize perceptual categories of related visual stimuli rapidly without explicit instruction. These results strongly indicate that visual categorization occurs at some earlier stage of feed-forward processing, presumably in temporal cortex, without top-down information from LPFC.

Increased neural resources recruitment in the intrinsic organization in major depression

Objective To investigate the functional connectivity (FC) pattern within an intrinsic functional organization, including both task-positive (TPN) and task-negative (TNN) networks, in major depressive disorder (MDD), and to examine relationships between the involved FCs and clinical variables. Methods Resting-state FC analyses were used to identify the component brain regions of the intrinsic organization and to investigate the FCs of the individual component regions in 18 first-episode, medication-naïve MDD and 20 healthy control subjects. Results We found that the intrinsic organization of the depressed group recruited more extensive regions than the control group. All of the altered FCs associated with the component regions increased in MDD. Specifically, in the TPN the increased FCs were primarily located in the bilateral lateral prefrontal cortices and the inferior parietal lobes, which have been implicated in attention and adaptive control. In the TNN, the increased FCs were primarily located in the posterior cingulate cortex and the medial orbitofrontal cortex, which are involved in episodic memory, self-reflection and emotional regulation. We also found increased anti-correlations between the two networks. Additionally, the strengths of the FCs associated with the lateral prefrontal cortices were found to be correlated with the duration of the depressive episode and the HDRS scores in the depressed patients. Limitations Clinical correlates of these abnormal FCs should be cautiously interpreted due to the small sample size in this study. Conclusions Abnormalities in the intrinsic organization may be an underlying basis for the pronounced and prolonged negative bias in processing emotional information observed in MDD.

FMRI in an oddball task: Effects of target‐to‐target interval

The amplitude of the P3 event-related potential (ERP) elicited by task-relevant target ("oddball") stimuli has been shown to vary in proportion to the length of time between targets. Here we use functional magnetic resonance imaging (fMRI) to identify neural systems modulated by target interval in a large sample of healthy adults (n=100) during performance of an auditory oddball task that included both target and novel stimuli. A positive relationship was found between target interval and hemodynamic activity in the anterior cingulate and in bilateral lateral prefrontal cortex, temporal-parietal junction, postcentral gryi, thalamus, and cerebellum. This modulation likely represents updating of the working memory template for the target stimuli. There was no such effect of novel interval, suggesting that neuronal modulation may only occur for task-relevant stimuli, possibly in the service of strategic resource allocation processes.