Disrupted hemodynamic response within dorsolateral prefrontal cortex during cognitive tasks among people with multiple sclerosis-related fatigue.

INTRODUCTION: Mental fatigue is an early and enduring symptom in persons with autoimmune disease particularly multiple sclerosis (MS). Neuromodulation has emerged as a potential treatment although optimal cortical targets have yet to be determined. We aimed to examine cortical hemodynamic responses within bilateral dorsolateral prefrontal cortex (dlPFC) and frontopolar areas during single and dual cognitive tasks in persons with MS-related fatigue compared to matched controls. METHODS: We recruited persons (15 MS and 12 age- and sex-matched controls) who did not have physical or cognitive impairment and were free from depressive symptoms. Functional near infrared spectroscopy (fNIRS) registered hemodynamic responses during the tasks. We calculated oxyhemoglobin peak, time-to-peak, coherence between channels (a potential marker of neurovascular coupling) and functional connectivity (z-score). RESULTS: In MS, dlPFC demonstrated disrupted hemodynamic coherence during both single and dual tasks, as evidenced by non-significant and negative correlations between fNIRS channels. In MS, reduced coherence occurred in left dorsolateral PFC during the single task but occurred bilaterally as the task became more challenging. Functional connectivity was lower during dual compared to single tasks in the right dorsolateral PFC in both groups. Lower z-score was related to greater feelings of fatigue. Peak and time-to-peak hemodynamic response did not differ between groups or tasks. CONCLUSIONS: Hemodynamic responses were inconsistent and disrupted in people with MS experiencing mental fatigue, which worsened as the task became more challenging. Our findings point to dlPFC, but not frontopolar areas, as a potential target for neuromodulation to treat cognitive fatigue.

Effect of dorsolateral prefrontal cortex structural measures on neuroplasticity and response to paired-associative stimulation in Alzheimer's dementia.

Long-term potentiation (LTP)-like activity can be induced by stimulation protocols such as paired associative stimulation (PAS). We aimed to determine whether PAS-induced LTP-like activity (PAS-LTP) of the dorsolateral prefrontal cortex (DLPFC) is associated with cortical thickness and other structural measures impaired in Alzheimer's dementia (AD). We also explored longitudinal relationships between these brain structures and PAS-LTP response after a repetitive PAS (rPAS) intervention. Mediation and regression analyses were conducted using data from randomized controlled trials with AD and healthy control participants. PAS-electroencephalography assessed DLPFC PAS-LTP. DLPFC thickness and surface area were acquired from T1-weighted magnetic resonance imaging. Fractional anisotropy and mean diffusivity (MD) of the superior longitudinal fasciculus (SLF)-a tract important to induce PAS-LTP-were measured with diffusion-weighted imaging. AD participants exhibited reduced DLPFC thickness and increased SLF MD. There was also some evidence that reduction in DLPFC thickness mediates DLPFC PAS-LTP impairment. Longitudinal analyses showed preliminary evidence that SLF MD, and to a lesser extent DLPFC thickness, is associated with DLPFC PAS-LTP response to active rPAS. This study expands our understanding of the relationships between brain structural changes and neuroplasticity. It provides promising evidence for a structural predictor to improving neuroplasticity in AD with neurostimulation. This article is part of a discussion meeting issue 'Long-term potentiation: 50 years on'.

Elucidating the underlying components of metacognitive systematic bias in the human dorsolateral prefrontal cortex and inferior parietal cortex.

Metacognitive systematic bias impairs human learning efficiency, which is characterized by the inconsistency between predicted and actual memory performance. However, the underlying mechanism of metacognitive systematic bias remains unclear in existing studies. In this study, we utilized judgments of learning task in human participants to compare the neural mechanism difference in metacognitive systematic bias. Participants encoded words in fMRI sessions that would be tested later. Immediately after encoding each item, participants predicted how likely they would remember it. Multivariate analyses on fMRI data demonstrated that working memory and uncertainty decisions are represented in patterns of neural activity in metacognitive systematic bias. The available information participants used led to overestimated bias and underestimated bias. Effective connectivity analyses further indicate that information about the metacognitive systematic bias is represented in the dorsolateral prefrontal cortex and inferior parietal cortex. Different neural patterns were found underlying overestimated bias and underestimated bias. Specifically, connectivity regions with the dorsolateral prefrontal cortex, anterior cingulate cortex, and supramarginal gyrus form overestimated bias, while less regional connectivity forms underestimated bias. These findings provide a mechanistic account for the construction of metacognitive systematic bias.

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.

Enhancing ventrolateral prefrontal cortex activation mitigates social pain and modifies subsequent social attitudes: Insights from TMS and fMRI.

Social pain, a multifaceted emotional response triggered by interpersonal rejection or criticism, profoundly impacts mental well-being and social interactions. While prior research has implicated the right ventrolateral prefrontal cortex (rVLPFC) in mitigating social pain, the precise neural mechanisms and downstream effects on subsequent social attitudes remain elusive. This study employed transcranial magnetic stimulation (TMS) integrated with fMRI recordings during a social pain task to elucidate these aspects. Eighty participants underwent either active TMS targeting the rVLPFC (n = 41) or control stimulation at the vertex (n = 39). Our results revealed that TMS-induced rVLPFC facilitation significantly reduced self-reported social pain, confirming the causal role of the rVLPFC in social pain relief. Functional connectivity analyses demonstrated enhanced interactions between the rVLPFC and the dorsolateral prefrontal cortex, emphasizing the collaborative engagement of prefrontal regions in emotion regulation. Significantly, we observed that negative social feedback led to negative social attitudes, whereas rVLPFC activation countered this detrimental effect, showcasing the potential of the rVLPFC as a protective buffer against adverse social interactions. Moreover, our study uncovered the impact role of the hippocampus in subsequent social attitudes, a relationship particularly pronounced during excitatory TMS over the rVLPFC. These findings offer promising avenues for improving mental health within the intricate dynamics of social interactions. By advancing our comprehension of the neural mechanisms underlying social pain relief, this research introduces novel intervention strategies for individuals grappling with social distress. Empowering individuals to modulate rVLPFC activation may facilitate reshaping social attitudes and successful reintegration into communal life.

The Important Role of the Right Dorsolateral Prefrontal Cortex in Conflict Adaptation: A Combined Voxel-Based Morphometry and Continuous Theta Burst Stimulation Study.

Humans can flexibly adjust their executive control to resolve conflicts. Conflict adaptation and conflict resolution are crucial aspects of conflict processing. Functional neuroimaging studies have associated the dorsolateral prefrontal cortex (DLPFC) with conflict processing, but its causal role remains somewhat controversial. Moreover, the neuroanatomical basis of conflict processing has not been thoroughly examined. In this study, the Stroop task, a well-established measure of conflict, was employed to investigate (1) the neuroanatomical basis of conflict resolution and conflict adaptation with the voxel-based morphometry analysis, (2) the causal role of DLPFC in conflict processing with the application of the continuous theta burst stimulation to DLPFC. The results revealed that the Stroop effect was correlated to the gray matter volume of the precuneus, postcentral gyrus, and cerebellum, and the congruency sequence effect was correlated to the gray matter volume of superior frontal gyrus, postcentral gyrus, and lobule paracentral gyrus. These findings indicate the neuroanatomical basis of conflict resolution and adaptation. In addition, the continuous theta burst stimulation over the right DLPFC resulted in a significant reduction in the Stroop effect of RT after congruent trials compared with vertex stimulation and a significant increase in the Stroop effect of accuracy rate after incongruent trials than congruent trials, demonstrating the causal role of right DLPFC in conflict adaptation. Moreover, the DLPFC stimulation did not affect the Stroop effect of RT and accuracy rate. Overall, our study offers further insights into the neural mechanisms underlying conflict resolution and adaptation.

Feasibility of training the dorsolateral prefrontal-striatal network by real-time fMRI neurofeedback.

Real-time fMRI neurofeedback (rt-fMRI NF) is a promising non-invasive technique that enables volitional control of usually covert brain processes. While most rt-fMRI NF studies so far have demonstrated the ability of the method to evoke changes in brain activity and improve symptoms of mental disorders, a recently evolving field is network-based functional connectivity (FC) rt-fMRI NF. However, FC rt-fMRI NF has methodological challenges such as respirational artefacts that could potentially bias the training if not controlled. In this randomized, double-blind, yoke-controlled, pre-registered FC rt-fMRI NF study with healthy participants (N = 40) studied over three training days, we tested the feasibility of an FC rt-fMRI NF approach with online global signal regression (GSR) to control for physiological artefacts for up-regulation of connectivity in the dorsolateral prefrontal-striatal network. While our pre-registered null hypothesis significance tests failed to reach criterion, we estimated the FC training effect at a medium effect size at the end of the third training day after rigorous control of physiological artefacts in the offline data. This hints at the potential of FC rt-fMRI NF for the development of innovative transdiagnostic circuit-specific interventional approaches for mental disorders and the effect should now be confirmed in a well-powered study.

Aching face and hand: the interoceptive attentiveness and social context in relation to empathy for pain.

This research explored how the manipulation of interoceptive attentiveness (IA) can influence the frontal (dorsolateral prefrontal cortex (DLPFC) and somatosensory cortices) activity associated with the emotional regulation and sensory response of observing pain in others. 20 individuals were asked to observe face versus hand, painful/non-painful stimuli in an individual versus social condition while brain hemodynamic response (oxygenated (O2Hb) and deoxygenated hemoglobin (HHb) components) was measured via functional Near-Infrared Spectroscopy (fNIRS). Images represented either a single person (individual condition) or two persons in social interaction (social condition) both for the pain and body part set of stimuli. The participants were split into experimental (EXP) and control (CNT) groups, with the EXP explicitly required to concentrate on its interoceptive correlates while observing the stimuli. Quantitative statistical analyses were applied to both oxy- and deoxy-Hb data. Firstly, significantly higher brain responsiveness was detected for pain in comparison to no-pain stimuli in the individual condition. Secondly, a left/right hemispheric lateralization was found for the individual and social condition, respectively, in both groups. Besides, both groups showed higher DLPFC activation for face stimuli presented in the individual condition compared to hand stimuli in the social condition. However, face stimuli activation prevailed for the EXP group, suggesting the IA phenomenon has certain features, namely it manifests itself in the individual condition and for pain stimuli. We can conclude that IA promoted the recruitment of internal adaptive regulatory strategies by engaging both DLPFC and somatosensory regions towards emotionally relevant stimuli.

Opioid antagonism modulates wanting-related frontostriatal connectivity.

Theoretical accounts distinguish between motivational ('wanting') and hedonic ('liking') dimensions of rewards. Previous animal and human research linked wanting and liking to anatomically and neurochemically distinct brain mechanisms, but it remains unknown how the different brain regions and neurotransmitter systems interact in processing distinct reward dimensions. Here, we assessed how pharmacological manipulations of opioid and dopamine receptor activation modulate the neural processing of wanting and liking in humans in a randomized, placebo-controlled, double-blind clinical trial. Reducing opioid receptor activation with naltrexone selectively reduced wanting of rewards, which on a neural level was reflected by stronger coupling between dorsolateral prefrontal cortex and the striatum under naltrexone compared with placebo. In contrast, reducing dopaminergic neurotransmission with amisulpride revealed no robust effects on behavior or neural activity. Our findings thus provide insights into how opioid receptors mediate neural connectivity related to specifically motivational, not hedonic, aspects of rewards.

Enhanced Temporal Coupling between Thalamus and Dorsolateral Prefrontal Cortex Mediates Chronic Low Back Pain and Depression.

Numerous neuroimaging studies have demonstrated that the brain plasticity is associated with chronic low back pain (cLBP). However, there is a lack of knowledge regarding the underlying mechanisms of thalamic pathways for chronic pain and psychological effects in cLBP caused by lumbar disc herniation (LDH). Combining psychophysics and magnetic resonance imaging (MRI), we investigated the structural and functional brain plasticity in 36 patients with LDH compared with 38 age- and gender-matched healthy controls. We found that (1) LDH patients had increased psychophysical disturbs (i.e., depression and anxiety), and depression (Beck-Depression Inventory, BDI) was found to be an outstanding significant factor to predict chronic pain (short form of the McGill Pain Questionnaire, SF-MPQ); (2) the LDH group showed significantly smaller fractional anisotropy values in the region of posterior corona radiate while gray matter volumes were comparable in both groups; (3) resting state functional connectivity analysis revealed that LDH patients exhibited increased temporal coupling between the thalamus and dorsolateral prefrontal cortex (DLPFC), which further mediate the relationship from chronic pain to depression. Our results emphasized that thalamic pathways underlying prefrontal cortex might play a key role in regulating chronic pain and depression of the pathophysiology of LDH.

Increased neural motor activation and functional reorganization in patients with idiopathic rapid eye movement sleep behavior disorder.

INTRODUCTION: Altered brain activity and functional reorganization patterns during self-initiated movements have been reported in early pre-motor and motor stages of Parkinson's disease. The aim of this study was to investigate whether similar alterations can be observed in patients with idiopathic REM-sleep behavior disorder (RBD). METHODS: 13 polysomnography-confirmed male and right-handed RBD patients and 13 healthy controls underwent a bilateral hand-movement fMRI task including internally selected (INT) and externally-guided (EXT) movement conditions for each hand. We examined functional activity and connectivity differences between groups and task-conditions, structural differences using voxel-based morphometry, as well as associations between functional activity and clinical variables. RESULTS: No group differences were observed in fMRI-task performance or in voxel-based morphometry. Both groups showed faster reaction times and exhibited greater neural activation when movements were internally selected compared to externally-guided tasks. Compared to controls, RBD patients displayed stronger activation in the dorsolateral prefrontal cortex and primary somatosensory cortex during INT-tasks, and in the right fronto-insular cortex during EXT-tasks performed with the non-dominant hand. Stronger activation in RBD patients was associated with cognitive and olfactory impairment. Connectivity analysis demonstrated overall less interregional coupling in patients compared to controls. In particular, patients showed reduced temporo-cerebellar, occipito-cerebellar and intra-cerebellar connectivity, but stronger connectivity in fronto-cerebellar and fronto-occipital pathways. CONCLUSION: The observed stronger activation during hand-movement tasks and connectivity changes in RBD may reflect early compensatory and reorganization patterns in order to preserve motor functioning. Our findings may contribute to a better understanding and prognosis of prodromal stages of α-synucleinopathies.

Polygenic risk for obsessive-compulsive disorder (OCD) predicts brain response during working memory task in OCD, unaffected relatives, and healthy controls.

Alterations in frontal and parietal neural activations during working memory task performance have been suggested as a candidate endophenotype of obsessive-compulsive disorder (OCD) in studies involving first-degree relatives. However, the direct link between genetic risk for OCD and neuro-functional alterations during working memory performance has not been investigated to date. Thus, the aim of the current functional magnetic resonance imaging (fMRI) study was to test the direct association between polygenic risk for OCD and neural activity during the performance of a numeric n-back task with four working memory load conditions in 128 participants, including patients with OCD, unaffected first-degree relatives of OCD patients, and healthy controls. Behavioral results show a significant performance deficit at high working memory load in both patients with OCD and first-degree relatives (p < 0.05). A whole-brain analysis of the fMRI data indicated decreased neural activity in bilateral inferior parietal lobule and dorsolateral prefrontal cortex in both patients and relatives. Most importantly, OCD polygenic risk scores predicted neural activity in orbitofrontal cortex. Results indicate that genetic risk for OCD can partly explain alterations in brain response during working memory performance, supporting the notion of a neuro-functional endophenotype for OCD.

Repeated anodal high-definition transcranial direct current stimulation over the left dorsolateral prefrontal cortex in mild cognitive impairment patients increased regional homogeneity in multiple brain regions.

Transcranial direct current stimulation (tDCS) can improve cognitive function. However, it is not clear how high-definition tDCS (HD-tDCS) regulates the cognitive function and its neural mechanism, especially in individuals with mild cognitive impairment (MCI). This study aimed to examine whether HD-tDCS can modulate cognitive function in individuals with MCI and to determine whether the potential variety is related to spontaneous brain activity changes recorded by resting-state functional magnetic resonance imaging (rs-fMRI). Forty-three individuals with MCI were randomly assigned to receive either 10 HD-tDCS sessions or 10 sham sessions to the left dorsolateral prefrontal cortex (L-DLPFC). The fractional amplitude of low-frequency fluctuation (fALFF) and the regional homogeneity (ReHo) was computed using rs-fMRI data from all participants. The results showed that the fALFF and ReHo values changed in multiple areas following HD-tDCS. Brain regions with significant decreases in fALFF values include the Insula R, Precuneus R, Thalamus L, and Parietal Sup R, while the Temporal Inf R, Fusiform L, Occipital Sup L, Calcarine R, and Angular R showed significantly increased in their fALFF values. The brain regions with significant increases in ReHo values include the Temporal Inf R, Putamen L, Frontal Mid L, Precentral R, Frontal Sup Medial L, Frontal Sup R, and Precentral L. We found that HD-tDCS can alter the intensity and synchrony of brain activity, and our results indicate that fALFF and ReHo analysis are sensitive indicators for the detection of HD-tDCS during spontaneous brain activity. Interestingly, HD-tDCS increases the ReHo values of multiple brain regions, which may be related to the underlying mechanism of its clinical effects, these may also be related to a potential compensation mechanism involving the mobilization of more regions to complete a function following a functional decline.

Functional localization and categorization of intentional decisions in humans: A meta-analysis of brain imaging studies.

Brain-imaging research on intentional decision-making often employs a "free-choice" paradigm, in which participants choose among options with identical values or outcomes. Although the medial prefrontal cortex has commonly been associated with choices, there is no consensus on the wider network that underlies diverse intentional decisions and behaviours. Our systematic literature search identified 35 fMRI/PET experiments using various free-choice paradigms, with appropriate control conditions using external instructions. An Activation Likelihood Estimate (ALE) meta-analysis showed that, compared with external instructions, intentional decisions consistently activate the medial and dorsolateral prefrontal cortex, the left insula and the inferior parietal lobule. We then categorized the studies into four different types according to their experimental designs: reactive motor intention, perceptual intention, inhibitory intention, and cognitive intention. We conducted conjunction and contrast meta-analyses to identify consistent and selective spatial convergence of brain activation within each specific category of intentional decision. Finally, we used meta-analytic decoding to probe cognitive processes underlying free choices. Our findings suggest that the neurocognitive process underlying intentional decision incorporates anatomically separated components subserving distinct cognitive and computational roles.

Ventrolateral prefrontal hemodynamic responses in autism spectrum disorder with and without depression.

In clinical settings, autism spectrum disorder (ASD) with comorbid depression is often difficult to diagnose, and should be considered in treatment. However, to our knowledge, no functional imaging study has examined the difference between ASD adolescents with and without comorbid depression. We aimed to compare the characteristics and prefrontal brain function of ASD with and without depression in order to identify a biological marker that can be used to detect the difference. Twenty-eight drug-naïve adolescents with ASD (14 ASD with and 14 ASD without depression) and 14 age- and gender-matched adolescents with typical development were evaluated using several variables. These included intelligence quotient, autism quotient, depression severity using the Beck Depression Inventory 2nd edition (BDI-II), and level of social functioning using the Social Adaptation Self-evaluation Scale (SASS). In addition, frontotemporal hemodynamic responses during a verbal fluency task (VFT) were measured using functional near-infrared spectroscopy (fNIRS). The ASD group, including both of the ASD with and ASD without depression groups, showed smaller hemodynamic responses than the typical development group in portions of the left dorsolateral prefrontal cortex (DLPFC), bilateral ventrolateral prefrontal cortex (VLPFC) and anterior part of the temporal cortex (aTC) during the VFT. Moreover, the smaller hemodynamic responses in the right VLPFC during the VFT in the ASD group were associated with the worse BDI-II and SASS scores. Furthermore, the ASD with depression group showed smaller hemodynamic responses in the right VLPFC during the VFT than the ASD without depression group in a direct comparison. Adolescents with ASD showed reduced activation in broad frontotemporal regions during a cognitive task compared with those with typical development. More specifically, the right VLPFC activation reflected the level of self-estimated depression and social functioning in the ASD subjects, and could be used to discriminate between ASD adolescents with and without depression.

Increased functional interaction within frontoparietal network during working memory task in major depressive disorder.

Abnormal fronto-parietal activation has been suggested as a neural underpinning of the working memory (WM) deficits in major depressive disorder (MDD). However, the potential interaction within the frontoparietal network during WM processing in MDD remains unclear. This study aimed to examine the role of abnormal functional interactions within frontoparietal network in the neuropathological mechanisms of WM deficits in MDD. A total of 40 MDD patients and 47 demographic matched healthy controls (HCs) were included. Functional magnetic resonance imaging and behavioral data were collected during numeric n-back tasks. The psychophysiological interaction and dynamic causal modelling methods were applied to investigate the connectivity within the frontoparietal network in MDD during n-back tasks. The psychophysiological interaction analysis revealed that MDD patients showed increased functional connectivity between the right inferior parietal lobule (IPL) and the right dorsolateral prefrontal cortex (dlPFC) compared with HCs during the 2-back task. The dynamic causal modelling analysis revealed that MDD patients had significantly increased forward modulation connectivity from the right IPL to the right dlPFC than HCs during the 2-back task. Partial correlation was used to calculate the relationship between connective parameters and psychological variables in the MDD group, which showed that the effective connectivity from right IPL to right dlPFC was correlated negatively with the sensitivity index d' of WM performances and positively with the depressive severity in MDD group. In conclusion, the abnormal functional and effective connectivity between frontal and parietal regions might contribute to explain the neuropathological mechanism of working memory deficits in major depressive disorder.

Metabolic alterations of the dorsolateral prefrontal cortex in sleep-related hypermotor epilepsy: A proton magnetic resonance spectroscopy study.

Sleep-related hypermotor epilepsy (SHE) is a focal epilepsy whose neurobiological underpinnings remain poorly understood. The present study aimed to identify possible neurochemical alterations in the dorsolateral prefrontal cortex (DLPFC) in participants with SHE using proton magnetic resonance spectroscopy (1 H MRS). Thirty-nine participants with SHE (mean age, 30.7 years ± 11.3 [standard deviation], 24 men) and 59 controls (mean age, 29.4 years ± 10.4, 29 men) were consecutively and prospectively recruited and underwent brain magnetic resonance imaging and 1 H MRS in the bilateral DLPFCs. Brain concentrations of metabolites, including N-acetyl aspartate (NAA), myo-inositol (mI), choline, creatine, the sum of glutamate and glutamine, glutathione (GSH) and γ-aminobutyric acid, were estimated with LCModel and corrected for the partial volume effect of cerebrospinal fluid using tissue segmentation. ANCOVA analyses revealed lower concentration of NAA in the left DLPFC in participants with SHE compared with controls. A significant difference of NAA concentration between DLPFC in the two hemispheres (left > right) was observed only in the control group. We further confirmed a higher GSH concentration in men than in women in SHE participants, which probably indicates that men are more susceptible to this disease. The mI concentration in the right DLPFC was negatively correlated with epilepsy duration. This study demonstrates that DLPFC is an important brain region involved in the pathophysiology of SHE, in which both neurons and astrocytes appear impaired, and the elevated GSH level may suggest an abnormality related to oxidative stress.

Neural representations of the amount and the delay time of reward in intertemporal decision making.

Numerous studies have examined the neural substrates of intertemporal decision-making, but few have systematically investigated separate neural representations of the two attributes of future rewards (i.e., the amount of the reward and the delay time). More importantly, no study has used the novel analytical method of representational connectivity analysis (RCA) to map the two dimensions' functional brain networks at the level of multivariate neural representations. This study independently manipulated the amount and delay time of rewards during an intertemporal decision task. Both univariate and multivariate pattern analyses showed that brain activity in the dorsomedial prefrontal cortex (DMPFC) and lateral frontal pole cortex (LFPC) was modulated by the amount of rewards, whereas brain activity in the DMPFC and dorsolateral prefrontal cortex (DLPFC) was modulated by the length of delay. Moreover, representational similarity analysis (RSA) revealed that even for the regions of the DMPFC that overlapped between the two dimensions, they manifested distinct neural activity patterns. In terms of individual differences, those with large delay discounting rates (k) showed greater DMPFC and LFPC activity as the amount of rewards increased but showed lower DMPFC and DLPFC activity as the delay time increased. Lastly, RCA suggested that the topological metrics (i.e., global and local efficiency) of the functional connectome subserving the delay time dimension inversely predicted individual discounting rate. These findings provide novel insights into neural representations of the two attributes in intertemporal decisions, and offer a new approach to construct task-based functional brain networks whose topological properties are related to impulsivity.

Functional impairment-based segmentation of anterior cingulate cortex in depression and its relationship with treatment effects.

In major depressive disorder (MDD), the anterior cingulate cortex (ACC) is widely related to depression impairment and antidepressant treatment response. The multiplicity of ACC subdivisions calls for a fine-grained investigation of their functional impairment and recovery profiles. We recorded resting state fMRI signals from 59 MDD patients twice before and after 12-week antidepressant treatment, as well as 59 healthy controls (HCs). With functional connectivity (FC) between each ACC voxel and four regions of interests (bilateral dorsolateral prefrontal cortex [DLPFC] and amygdalae), subdivisions with variable impairment were identified based on groups' dissimilarity values between MDD patients before treatment and HC. The ACC was subdivided into three impairment subdivisions named as MedialACC, DistalACC, and LateralACC according to their dominant locations. Furthermore, the impairment pattern and the recovery pattern were measured based on group statistical analyses. DistalACC impaired more on its FC with left DLPFC, whereas LateralACC showed more serious impairment on its FC with bilateral amygdalae. After treatment, FCs between DistalACC and left DLPFC, and between LateralACC and right amygdala were normalized while impaired FC between LateralACC and left amygdala kept dysfunctional. Subsequently, FC between DistalACC and left DLPFC might contribute to clinical outcome prediction. Our approach could provide an insight into how the ACC was impaired in depression and partly restored after antidepressant treatment, from the perspective of the interaction between ACC subregions and critical frontal and subcortical regions.