Resting-state neural correlates of individual differences in ignored experience and its deleterious effect.

Uncovering the neural mechanisms of ostracism experience (including its subclasses of excluded and ignored experiences) is important. However, the resting-state functional brain substrates responsible for individual differences in ostracism experience and its negative effects remain largely undefined. This study explored these issues in a sample of 198 Chinese college students by assessing the amplitude of low-frequency fluctuations and functional connectivity. The findings indicated a positive correlation between ignored experience and the amplitude of low-frequency fluctuations in the right superior frontal gyrus and the functional connectivity between the right superior frontal gyrus and left cerebellum posterior lobe. Additionally, a negative correlation was found between ignored experience and the functional connectivity between the right superior frontal gyrus and the bilateral insula as well as the bilateral inferior parietal lobule. Moreover, the mediation analysis demonstrated that the effects of the functional connectivities of right superior frontal gyrus-left cerebellum posterior lobe and right superior frontal gyrus-right inferior parietal lobule on revenge intention were mediated by ignored experience. Our study offers novel insights into the neural correlates of both individual variations in ignored experience and its typical deleterious effect. These results could deepen our understanding of individual differences in negative experiences and inspire the development of targeted interventions for social stress from the perspective of the brain.

Memantine for the patients with mild cognitive impairment in Parkinson's disease: a pharmacological fMRI study.

BACKGROUND: Mild cognitive impairment in Parkinson's disease (PD-MCI) is associated with an increased risk of cognitive decline. PD-MCI is characterized by impairments in executive function and visuospatial recognition. The visuospatial n-back test is useful for assessing both domains. The 0-back test reflects visuospatial recognition, while the 1-back and 2-back tests reflect working memory. Cholinesterase inhibitors are effective in the treatment of PD-MCI and dementia in PD (PDD). Although some studies have reported the efficacy of memantine for PDD, the therapeutic efficacy of memantine in patients with PD-MCI remains uncertain. METHODS: This study aimed to investigate the effects of memantine on brain function in patients with PD-MCI, using a randomized double-blinded crossover protocol and functional MRI (fMRI). Ten patients who completed 16 weeks of follow-up were included. They were randomly assigned to either the memantine or placebo. Patients in the memantine group received 5 mg/day of memantine in the first week. The memantine dose was increased by 5 mg/day per week, until a final dose of 20 mg/day. Patients in the placebo group received the placebo following the same regimen as memantine. After the intervention, they underwent a 4 weeks washout period. Following the crossover protocol, a second intervention was conducted after the washout period. In each intervention, fMRI and neuropsychological tests were performed at the maximum dose period. Comparing the memantine and placebo groups, we investigated difference in the brain regions using the visuospatial n-back test. RESULTS: There were no significant regions enhanced by memantine comparing with placebo at any load of n-back tests. In contrast, exploring regions reduced by memantine, we found significant reduction of activations within right lingual gyrus and left superior frontal gyrus in comparison between 2-back and 0-back test. A number of correct answers of the 2-back test and time to complete Trail Making Test-A were worse during memantine intervention. CONCLUSIONS: Memantine did not improve visuospatial working memory of the patients with PD-MCI. Treatment for PD should be planned carefully considering the impact on cognitive function. Further study is needed to establish new therapeutic strategy. TRIAL REGISTRATION: UMIN000046104. Retrospectively registered. First registration date: 28 Sept 2017.

The neural mechanisms underlying the modulation of attentional deployment on emotional stability.

Emotional stability, the change of emotion response among situations, was associated with mental illness, such as depression. The current study aimed to explore the modulation of attentional deployment on emotional stability by combining functional magnetic resonance imaging (fMRI) and a sequential risk-taking task. During the task, participants were asked to open a series of boxes consecutively and decided when to stop. Each box contained a reward, except one containing a devil to zero reward in the trial. When participants stopped, both collected gains and missed chances were revealed. The attentional deployment was manipulated during the outcome feedback, i.e., inducing participants to focus on the good part (GF context) or the bad part (MF context) of the decision outcome. Besides, the Control context was also set, in which the attentional deployment was not manipulated. The behavioral results showed that the emotional stability was stronger in GF context relative to MF and Control contexts. At the neural level, with outcomes getting better, activations of ventral striatum (VS) and superior frontal gyrus (SFG) increased faster in GF context than that in MF and Control contexts. In addition, in GF context, the changing of SFG activation with outcomes getting better was associated with emotional stability. The current study highlighted that focusing on the good part of decision outcomes could enhance emotional stability effectively and SFG played a vital role in this process.

The alterations of degree centrality in the frontal lobe of patients with panic disorder.

Objective: The brain network in panic disorder (PD) is still an intriguing issue for research. In this study, we hoped to investigate the role of DC (degree centrality) for the pathophysiology of PD, especially for the fear network. Methods: We enrolled 60 patients with PD and 60 controls in the current study. The gender and age were matched for two groups. All participants received the resting-state functional magnetic resonance imaging to survey the baseline brain activity. Then the DC values of all participants were using REST toolbox. We also compared the DC values between PD and controls. The statistical threshold was set as FDR (false discovery rate) < 0.05. Results: The DC values were significantly lower in the right superior frontal gyrus of PD patients compared to controls (FDR < 0.05). In addition, a negative correlation between the DC values and panic severity was observed in the right superior frontal gyrus and left inferior frontal gyrus. However, there was no significant association between the DC values and illness duration. Conclusion: The DC seemed significantly altered in the frontal lobe of PD patients. The role of the frontal lobe might be more emphasized in the pathophysiology research for PD.

Altered intrinsic default mode network functional connectivity in patients with remitted geriatric depression and amnestic mild cognitive impairment.

OBJECTIVES: Patients with geriatric depression exhibit a spectrum of symptoms ranging from mild to severe cognitive impairment which could potentially lead to the development of Alzheimer's disease (AD). The aim of the study is to assess the alterations of the default mode network (DMN) in remitted geriatric depression (RGD) patients and whether it could serve as an underlying neuropathological mechanism associated with the risk of progression of AD. DESIGN: Cross-sectional study. PARTICIPANTS: A total of 154 participants, comprising 66 RGD subjects (which included 27 patients with comorbid amnestic mild cognitive impairment [aMCI] and 39 without aMCI [RGD]), 45 aMCI subjects without a history of depression (aMCI), and 43 matched healthy comparisons (HC), were recruited. MEASUREMENTS: All participants completed neuropsychological tests and underwent resting-state functional magnetic resonance imaging (fMRI). Posterior cingulate cortex (PCC)-seeded DMN functional connectivity (FC) along with cognitive function were compared among the four groups, and correlation analyses were conducted. RESULTS: In contrast to HC, RGD, aMCI, and RGD-aMCI subjects showed significant impairment across all domains of cognitive functions except for attention. Furthermore, compared with HC, there was a similar and significant decrease in PCC-seed FC in the bilateral medial superior frontal gyrus (M-SFG) in the RGD, aMCI, and RGD-aMCI groups. CONCLUSIONS: The aberrations in rsFC of the DMN were associated with cognitive deficits in RGD patients and might potentially reflect an underlying neuropathological mechanism for the increased risk of developing AD. Therefore, altered connectivity in the DMN could serve as a potential neural marker for the conversion of geriatric depression to AD.

Structural atrophy of the right superior frontal gyrus in adolescents with severe irritability.

Severe irritability is common in youths with psychiatric disorders and results in significant dysfunction across domains (academic, social, and familial). Prior structural MRI studies in the pediatric population demonstrated that aberrations of cortical thickness (CT) and gray matter volume (GMV) in the fronto-striatal-temporal regions which have been associated with irritability. However, the directions of the correlations between structural alteration and irritability in the individual indices were not consistent. Thus, we aim to address this by implementing comprehensive assessments of CT, GMV, and local gyrification index (LGI) simultaneously in youths with severe levels of irritability by voxel-based morphometry and surface-based morphometry. One hundred and eight adolescents (46 youths with severe irritability and 62 healthy youths, average age = 14.08 years, standard deviation = 2.36) were scanned with a T1-weighted MRI sequence. The severity of irritability was measured using the affective reactivity index. In youths with severe irritability, there was decreased CT, GMV, and LGI in the right superior frontal gyrus (SFG) compared to healthy youths, and negative correlations between these indices of the SFG and irritability. Our findings suggest that structural deficits in the SFG, potentially related to its role in inhibitory control, may be critical for the neurobiology of irritability.

Cascade process mediated by left hippocampus and left superior frontal gyrus affects relationship between aging and cognitive dysfunction.

BACKGROUND: Cognitive function declines with age and has been shown to be associated with atrophy in some brain regions, including the prefrontal cortex. However, the details of the relationship between aging and cognitive dysfunction are not well understood. METHODS: Across a wide range of ages (24- to 85-years-old), this research measured the gray matter volume of structural magnetic resonance imaging data in 39 participants, while some brain regions were set as mediator variables to assess the cascade process between aging and cognitive dysfunction in a path analysis. RESULTS: Path analysis showed that age affected the left hippocampus, thereby directly affecting the left superior frontal gyrus. Furthermore, the gyrus directly affected higher order flexibility and maintenance abilities calculated as in the Wisconsin card sorting test, and the two abilities affected the assessment of general cognitive function. CONCLUSION: Our finding suggests that a cascade process mediated by the left hippocampus and left superior frontal gyrus is involved in the relationship between aging and cognitive dysfunction.

Individual differences in envy experienced through perspective-taking involves functional connectivity of the superior frontal gyrus.

Envy is the painful or resentful awareness of another's advantage combined with a desire to possess that same advantage. Recent neuroscientific research has begun to shed light on the brain regions that process the experience of envy, including regions of the prefrontal cortex involved in emotional processing and social cognition. It is still unclear, however, which regions of the brain are functionally connected during the experience of envy. We recorded functional neuroimaging data while inducing simulated envy in participants, experienced through a perspective-taking hypothetical scenario task. In this task, participants took the perspective of a protagonist portrayed in a written description and compared themselves to either i) a self-similar/superior individual, ii) a self-dissimilar/superior individual, or iii) a self-dissimilar/average individual. During each comparison, participants also reported how much envy they experienced while taking the protagonists perspective. We demonstrate an inverse relationship in the connectivity of the left superior frontal gyrus to both the right supramarginal gyrus and the precuneus with respect to self-reported envy ratings across participants. In other words, we show that the greater the functional connectivity that the left superior frontal gyrus shares with the right supramarginal gyrus and precuneus, the less reported envy a participant experiences. Overall, our results are in line with previous research implicating the superior frontal gyrus in the reappraisal of negative emotions and extend these findings by showing this region is also involved in modulating the simulated experience of the social comparative, negative emotion of envy.

Disrupted alertness and related functional connectivity in patients with focal impaired awareness seizures in temporal lobe epilepsy.

OBJECTIVE: Focal impaired awareness seizures are common in temporal lobe epilepsy (TLE). The cognitive impairment associated with this type of seizure is unclear. Alertness is a fundamental aspect of cognition. The locus coeruleus (LC) is closely related to alertness. We aimed to assess the impairment in alertness and LC-related alertness network in patients with focal impaired awareness seizures. METHODS: Patients with unilateral TLE were grouped into the only focal impaired awareness seizure group (focal group, n = 19) and the focal impaired awareness seizure with focal to bilateral tonic-clonic seizure (FBTCS) group (FBTCS group, n = 19) and compared with matched healthy controls (HC, n = 19). Alertness was assessed with the attention network test. Functional magnetic resonance imaging (fMRI) was used to construct an alertness-related LC-based functional connectivity (FC) network. RESULTS: The focal group exhibited impaired tonic and phasic alertness and exhibited a decreased trend of LC-based FC to the left superior frontal gyrus (SFG). The FBTCS group exhibited impaired tonic alertness, phasic alertness, and alertness efficiency. No significant difference or trend in LC-based FC was found in the FBTCS group. SIGNIFICANCE: This study reveals disrupted alertness and alertness-related LC-based FC in patients with focal impaired awareness seizures. Our results further demonstrate that the patterns of impaired alertness and of changed LC-based FC were not significantly different between focal impaired awareness seizures and FBTCS.

A controlled comparison of thickness, volume and surface areas from multiple cortical parcellation packages.

BACKGROUND: Cortical parcellation is an essential neuroimaging tool for identifying and characterizing morphometric and connectivity brain changes occurring with age and disease. A variety of software packages have been developed for parcellating the brain's cortical surface into a variable number of regions but interpackage differences can undermine reproducibility. Using a ground truth dataset (Edinburgh_NIH10), we investigated such differences for grey matter thickness (GMth), grey matter volume (GMvol) and white matter surface area (WMsa) for the superior frontal gyrus (SFG), supramarginal gyrus (SMG), and cingulate gyrus (CG) from 4 parcellation protocols as implemented in the FreeSurfer, BrainSuite, and BrainGyrusMapping (BGM) software packages. RESULTS: Corresponding gyral definitions and morphometry approaches were not identical across the packages. As expected, there were differences in the bordering landmarks of each gyrus as well as in the manner in which variability was addressed. Rostral and caudal SFG and SMG boundaries differed, and in the event of a double CG occurrence, its upper fold was not always addressed. This led to a knock-on effect that was visible at the neighbouring gyri (e.g., knock-on effect at the SFG following CG definition) as well as gyral morphometric measurements of the affected gyri. Statistical analysis showed that the most consistent approaches were FreeSurfer's Desikan-Killiany-Tourville (DKT) protocol for GMth and BrainGyrusMapping for GMvol. Package consistency varied for WMsa, depending on the region of interest. CONCLUSIONS: Given the significance and implications that a parcellation protocol will have on the classification, and sometimes treatment, of subjects, it is essential to select the protocol which accurately represents their regions of interest and corresponding morphometrics, while embracing cortical variability.

Apolipoprotein ε4 is associated with better cognitive control allocation in healthy young adults.

Many gene variants may impair our health and cognitive abilities at old age, but some of them paradoxically improve the same or similar functions at much younger age (antagonistic pleiotropy hypothesis). Such a diametric pattern may also hold true for the ancestral Apolipoprotein E (APOE) ε4 allele, which increases the risk for Alzheimer's disease and cognitive decline in old age, but may benefit (pre)frontal (executive) functions in young carriers. We therefore investigated potential cognitive benefits of the risk allele on cognitive control capacities and top-down control allocation ("metacontrol") in n = 190 healthy young adults. On a behavioral level, we found young APOE ε4 carriers to better adapt to different degrees of cognitive control requirements, with superior performance in case of high control demands. On a neurophysiological level, these group differences were reflected by modulations of the N450 component, which were rooted in activation differences of the superior frontal gyrus (SFG, BA8). Taken together, our results suggest that young ε4 carriers are more efficient than non-carriers at allocating cognitive control resources based on the actual task requirements (i.e. metacontrol), as they seem to experience less conflict/exert less effort and recruit fewer additional prefrontal areas when task set complexity increases. We further found that ε2 carriers processed implicit spatial stimulus features to a stronger degree than ε3 and ε4 carriers, but failed to benefit from this, as the additional information likely increased response selection conflicts. This finding should however be treated with ample caution as the group of ε2 carriers was comparatively small.

Time-dependent motor memory representations in prefrontal cortex.

How memories evolve over time is fundamental for understanding memory. Hippocampus-dependent episodic memories are generally assumed to undergo a time-dependent neural reorganization involving an increased reliance on neocortical areas. Yet, whether other forms of memory undergo a similar reorganization over time remains unclear. Here, we examined whether the neural underpinnings of motor sequence memories change over time. Participants were trained on a motor sequence learning task. Either 1d or 28d later, they performed a retention test for this task in the fMRI scanner. Sequence-specific motor memory was observed both 1d and 28d after initial training. Bayesian second-level fMRI analyses suggested a higher probability for task activity in the middle frontal gyrus and frontal pole 28d compared to 1d after initial motor learning. Searchlight representational similarity analysis indicated that areas in middle and superior frontal cortex were more involved in differentiating between multivariate activity patterns for old motor sequence memories and newly learned motor sequences in the 28d-group compared to the 1d-group. This increased involvement of lateral frontal areas during the task after 28 days was not paralleled by a decrease in those areas that were involved in performing the motor sequence retention task after 1d. These novel findings provide insights into how memories beyond the hippocampus evolve over time.

Stress and the brain: Perceived stress mediates the impact of the superior frontal gyrus spontaneous activity on depressive symptoms in late adolescence.

Identifying factors for the prediction of depression is a long-standing research topic in psychiatry and psychology. Perceived stress, which reflects the tendency to appraise one's life situations as stressful and overwhelming, has emerged as a stable predictor for depressive symptoms. However, the neurobiological bases of perceived stress and how perceived stress influences depressive symptoms in the healthy brain remain largely unknown. Here, we investigated these issues in 217 healthy adolescents by estimating the fractional amplitude of low-frequency fluctuations (fALFFs) via resting-state functional magnetic resonance imaging. A whole-brain correlation analysis showed that higher levels of perceived stress were associated with greater fALFF in the left superior frontal gyrus (SFG), which is a core brain region for cognitive control and emotion regulation-related processes. Mediation analysis further indicated that perceived stress mediated the link between the fALFF in the left SFG and depressive symptoms. Importantly, our results remained significant even when excluding the influences of head motion, anxiety, SFG gray matter structure, and school environment. Altogether, our findings suggested that the fALFF in the left SFG is a neurofunctional marker of perceived stress in adolescents and revealed a potential indirect effect of perceived stress on the association between the SFG spontaneous activity and depressive symptoms.

Stimulating Multiple-Demand Cortex Enhances Vocabulary Learning.

It is well established that networks within multiple-demand cortex (MDC) become active when diverse skills and behaviors are being learnt. However, their causal role in learning remains to be established. In the present study, we first performed functional magnetic resonance imaging on healthy female and male human participants to confirm that MDC was most active in the initial stages of learning a novel vocabulary, consisting of pronounceable nonwords (pseudowords), each associated with a picture of a real object. We then examined, in healthy female and male human participants, whether repetitive transcranial magnetic stimulation of a frontal midline node of the cingulo-opercular MDC affected learning rates specifically during the initial stages of learning. We report that stimulation of this node, but not a control brain region, substantially improved both accuracy and response times during the earliest stage of learning pseudoword-object associations. This stimulation had no effect on the processing of established vocabulary, tested by the accuracy and response times when participants decided whether a real word was accurately paired with a picture of an object. These results provide evidence that noninvasive stimulation to MDC nodes can enhance learning rates, thereby demonstrating their causal role in the learning process. We propose that this causal role makes MDC candidate target for experimental therapeutics; for example, in stroke patients with aphasia attempting to reacquire a vocabulary.SIGNIFICANCE STATEMENT Learning a task involves the brain system within which that specific task becomes established. Therefore, successfully learning a new vocabulary establishes the novel words in the language system. However, there is evidence that in the early stages of learning, networks within multiple-demand cortex (MDC), which control higher cognitive functions, such as working memory, attention, and monitoring of performance, become active. This activity declines once the task is learnt. The present study demonstrated that a node within MDC, located in midline frontal cortex, becomes active during the early stage of learning a novel vocabulary. Importantly, noninvasive brain stimulation of this node improved performance during this stage of learning. This observation demonstrated that MDC activity is important for learning.

Longitudinal relationships among depressive symptoms, cortisol, and brain atrophy in the neocortex and the hippocampus.

OBJECTIVE: Depression is associated with accelerated aging and age-related diseases. However, mechanisms underlying this relationship remain unclear. The aim of this study was to longitudinally assess the link between depressive symptoms, brain atrophy, and cortisol levels. METHOD: Participants from the Betula prospective cohort study (mean age = 59 years, SD = 13.4 years) underwent clinical, neuropsychological and brain 3T MRI assessments at baseline and a 4-year follow-up. Cortisol levels were measured at baseline in four saliva samples. Cortical and hippocampal atrophy rates were estimated and compared between participants with and without depressive symptoms (n = 81) and correlated with cortisol levels (n = 49). RESULTS: Atrophy in the left superior frontal gyrus and right lingual gyrus developed in parallel with depressive symptoms, and in the left temporal pole, superior temporal cortex, and supramarginal cortex after the onset of depressive symptom. Depression-related atrophy was significantly associated with elevated cortisol levels. Elevated cortisol levels were also associated with widespread prefrontal, parietal, lateral, and medial temporal atrophy. CONCLUSION: Depressive symptoms and elevated cortisol levels are associated with atrophy of the prefrontal and limbic areas of the brain.

Apathy is related to reduced activation in cognitive control regions during set-shifting.

Apathy is a prominent and influential symptom in several neurological and psychiatric disorders, but it also occurs in the healthy population. It has considerable impact on daily life functioning, in clinical as well as healthy samples. Even though cognitive control is thought to be disrupted in people with apathy, the exact neural underpinnings of apathy remain unclear. Because flexible shifting between behaviors (set-shifting) is crucial for goal-directed behavior, disruptions in set-shifting may underlie apathy. In this study, the neural correlates of apathy during set-shifting were studied in 34 healthy participants with varying levels of apathy, measured by the Apathy Evaluation Scale. During functional MRI scanning participants performed a set-shifting task, distinguishing between behavioral switches (a change in response to different stimuli), cognitive switches (a change in response rule), and salience decoupling (detecting a change in relevant stimuli). Regression analysis was used to assess the relationship between apathy and brain activation. Results showed that higher apathy scores were related to reduced activation in the medial superior frontal gyrus and cerebellum (Crus I/II) during cognitive set-shifting, but not behavioral shifting and salience decoupling. No relationship between apathy and accuracy or response time was found. These results support the idea that alterations in the neural basis of cognitive control, especially cognitive set-shifting, may contribute to apathy. Hum Brain Mapp 38:2722-2733, 2017. © 2017 Wiley Periodicals, Inc.

Vertical Parasagittal Hemispherotomy.

Hemispherotomy is a surgical procedure aimed at the treatment of hemispheric epilepsy. Hemispherotomy disconnects the commissural fibers, projecting fibers, and limbic system while preserving most of the brain parenchyma, unlike conventional hemispherectomy.1 Hemispherotomy is one of most complicated operations currently used in epilepsy surgery and requires a high-level understanding of the intrinsic neuroanatomy. Generally, 2 main techniques are applied in hemispherotomy: lateral hemispherotomy and vertical hemispherotomy.2,3 Vertical hemispherotomy was developed after the lateral technique. Despite a deeper, narrower surgical corridor, vertical hemispherotomy requires a smaller craniotomy and a shorter disconnection line and allows easier disconnection of the insula than the lateral approach.1 In performing vertical hemispherotomy, 2 options are available: the interhemispheric approach4 and the parasagittal approach.3 With the parasagittal approach, the lateral ventricle is opened and entered via superior frontal gyrus. To ease the surgery and minimize the operation time, we apply "partial superior frontal gyrus removal." This procedure is useful to widen a shallower surgical field while skipping the need for interhemispheric dissection. Total callosotomy is then performed via the lateral ventricle. To disconnect limbic system, we used the technique following the falx and tentorial edge as a landmark.5 Here, we present our surgical steps for parasagittal hemispherotomy in a 5-month-old girl diagnosed as hemimegalencephaly (Figures 1-8).

Relationships between Grey Matter Volume in the Bilateral Superior Frontal Gyrus and Reactive Aggression Varied by Level of Traditional Masculinity.

Although previous behavioral studies have associated reactive aggression (RA) and proactive aggression (PA) with traditional masculinity, further investigation is needed into the traditional masculinity-linked neuroanatomical characteristics of RA and PA. This study analyzed the traditional masculinity-by-aggression interaction in 705 participants (350 men) by measuring grey matter volume (GMV). We have expanded on previous studies and found that traditional masculinity was not associated with RA and PA when not controlled for traditional femininity. However, the association appeared when controlling for it. Furthermore, we found significant traditional masculinity-by-RA interactions on the GMV in the bilateral superior frontal gyrus, a region known to be involved in cognitive control. When traditional masculinity scores were 1 standard deviation above the mean, there was a positive correlation between RA and the GMV in the bilateral superior frontal gyrus. Conversely, when traditional masculinity scores were 1 standard deviation below the mean, there was a negative correlation between RA and the GMV in the region. However, no traditional masculinity-linked neuroanatomical characteristics of PA were found. The results indicated that individuals with high/low traditional masculinity perceived RA as a different outcome (gain or loss) of self-control. The results supported an opportunity to develop prevention or intervention strategies for RA.

Functional decoding and meta-analytic connectivity modeling in thyroid-associated ophthalmopathy.

Background: Thyroid-associated ophthalmopathy (TAO) is an orbital disease closely related to thyroid disease with a long-lasting duration that can be blinding and disabling. Recently, structural and functional neuroimaging studies have been performed in TAO patients, but studies have reported inconsistent results. This quantitative meta-analysis was conducted to identify convergent patterns of abnormal brain function among different studies in TAO. Methods: We searched PubMed, EMBASE, Cochrane, and Web of Science, performed reference tracking, and retrieved 15 eligible studies. Peak coordinates were extracted from these studies and subsequently tested for convergence using activation likelihood estimation (ALE). Results: Compared to healthy subjects, resting-state brain activity in the whole brain of TAO patients was significantly increased in the left superior frontal gyrus (SFG) and decreased in the left cuneus/precuneus. Functional decoding analysis of the BrainMap database revealed that these regions are predominantly associated with cognitive and emotional impairment. In this study, task-related meta-analytic connectivity modeling (MACM) analysis was used to describe the connectivity and function of the two seed regions. Significant coactivation of these regions was found primarily in the bilateral superior parietal lobule, medial frontal gyrus, left fusiform gyrus, left cingulate gyrus, supplementary motor area and thalamus. Conclusion: Our findings underscore the role of the SFG and the cuneus/precuneus in the pathophysiology of TAO, highlighting the crucial impact of working memory deficits.

Dose response of transcranial near infrared light stimulation on brain functional connectivity and cognition in older adults-A randomized comparison.

Photobiomodulation, also called low-level light therapy, has been reported in animal studies to have an effect on brain activity and cognition. However, studies in humans regarding its effect on cognition and brain functional connectivity, and the required dose threshold for achieving the same have been very limited. We compared the effects of different doses of photobiomodulation (PBM) on cognition and resting state brain functional connectivity in 25 cognitively normal adults aged 55-70 years. They were randomized to a single session of the sham group, "low-dose" and "high-dose" groups receiving NIR light with transcranial fluence of 26 and 52 J/cm2 respectively, and intranasal fluence of 9 and 18 J/cm2 respectively. There was a significant increase in resting state functional connectivity of the left superior frontal gyrus (SFG) with the left planum temporale (PT), p = 0.0016, and with the left inferior frontal gyrus, pars triangularis, p = 0.0235 in the "high-dose" group only compared to the "sham" group. There was also a significant improvement in visual search and processing speed (p = 0.012) in the "high-dose" group. Replication of these findings in an adequately powered randomized sham-controlled study in healthy older adults can pave the way for clinical application of NIRL as a therapeutic modality in patients with Alzheimer's disease.