Bilateral Inferior Parietal Lobule Research Articles

Causal Roles of Ventral and Dorsal Neural Systems for Automatic and Control Self-Reference Processing: A Function Lesion Mapping Study.

Background: Humans perceive and interpret the world through the lens of self-reference processes, typically facilitating enhanced performance for the task at hand. However, this research has predominantly emphasized the automatic facet of self-reference processing, overlooking how it interacts with control processes affecting everyday situations. Methods: We investigated this relationship between automatic and control self-reference processing in neuropsychological patients performing self-face perception tasks and the Birmingham frontal task measuring executive functions. Results: Principal component analysis across tasks revealed two components: one loaded on familiarity/orientation judgments reflecting automatic self-reference processing, and the other linked to the cross task and executive function indicating control processing requirements. Voxel-based morphometry and track-wise lesion-mapping analyses showed that impairments in automatic self-reference were associated with reduced grey matter in the ventromedial prefrontal cortex and right inferior temporal gyrus, and white matter damage in the right inferior fronto-occipital fasciculus. Deficits in executive control were linked to reduced grey matter in the bilateral inferior parietal lobule and left anterior insula, and white matter disconnections in the left superior longitudinal fasciculus and arcuate fasciculus. Conclusions: The causal evidence suggests that automatic and control facets of self-reference processes are subserved by distinct yet integrated ventral prefrontal-temporal and dorsal frontal-parietal networks, respectively.

Neural correlates of musical timbre: an ALE meta-analysis of neuroimaging data.

Timbre is a central aspect of music that allows listeners to identify musical sounds and conveys musical emotion, but also allows for the recognition of actions and is an important structuring property of music. The former functions are known to be implemented in a ventral auditory stream in processing musical timbre. While the latter functions are commonly attributed to areas in a dorsal auditory processing stream in other musical domains, its involvement in musical timbre processing is so far unknown. To investigate if musical timbre processing involves both dorsal and ventral auditory pathways, we carried out an activation likelihood estimation (ALE) meta-analysis of 18 experiments from 17 published neuroimaging studies on musical timbre perception. We identified consistent activations in Brodmann areas (BA) 41, 42, and 22 in the bilateral transverse temporal gyri, the posterior superior temporal gyri and planum temporale, in BA 40 of the bilateral inferior parietal lobe, in BA 13 in the bilateral posterior Insula, and in BA 13 and 22 in the right anterior insula and superior temporal gyrus. The vast majority of the identified regions are associated with the dorsal and ventral auditory processing streams. We therefore propose to frame the processing of musical timbre in a dual-stream model. Moreover, the regions activated in processing timbre show similarities to the brain regions involved in processing several other fundamental aspects of music, indicating possible shared neural bases of musical timbre and other musical domains.

Inner sense of rhythm: percussionist brain activity during rhythmic encoding and synchronization.

The main objective of this research is to explore the core cognitive mechanisms utilized by exceptionally skilled percussionists as they navigate complex rhythms. Our specific focus is on understanding the dynamic interactions among brain regions, respectively, related to externally directed cognition (EDC), internally directed cognition (IDC), and rhythm processing, defined as the neural correlates of rhythm processing (NCRP). The research involved 26 participants each in the percussionist group (PG) and control group (CG), who underwent task-functional magnetic resonance imaging (fMRI) sessions focusing on rhythm encoding and synchronization. Comparative analyses were performed between the two groups under each of these conditions. Rhythmic encoding showed decreased activity in EDC areas, specifically in the right calcarine cortex, left middle occipital gyrus, right fusiform gyrus, and left inferior parietal lobule, along with reduced NCRP activity in the left dorsal premotor, right sensorimotor cortex, and left superior parietal lobule. During rhythmic synchronization, there was increased activity in IDC areas, particularly in the default mode network, and in NCRP areas including the left inferior frontal gyrus and bilateral putamen. Conversely, EDC areas like the right dorsolateral prefrontal gyrus, right superior temporal gyrus, right middle occipital gyrus, and bilateral inferior parietal lobule showed decreased activity, as did NCRP areas including the bilateral dorsal premotor cortex, bilateral ventral insula, bilateral inferior frontal gyrus, and left superior parietal lobule. PG's rhythm encoding is characterized by reduced cognitive effort compared to CG, as evidenced by decreased activity in brain regions associated with EDC and the NCRP. Rhythmic synchronization reveals up-regulated IDC, down-regulated EDC involvement, and dynamic interplay among regions with the NCRP, suggesting that PG engages in both automatic and spontaneous processing simultaneously. These findings provide valuable insights into expert performance and present opportunities for improving music education.

Harsh, unpredictable childhood environments are associated with inferior frontal gyrus connectivity and binge eating tendencies in late adolescents

Harsh, unpredictable childhood environments (HUCE) are associated with obesity older in life, but knowledge of how HUCE affect binge eating tendencies is lacking. Five hundred and one late adolescents aged 16–22 were recruited to finish resting state functional magnetic resonance imaging scan, behavioral measures including retrospective recall of childhood environmental harshness and unpredictability, binge eating tendencies and demographics. Three hundred and seventy-six of participants further completed the computerized visual probe task designed to evaluate attentional engagement towards high and low calorie food. As right inferior frontal gyrus (IFG) was the key nodes that related to both early life adversity and binge eating tendencies, it was treated as the interest region in the dynamic functional connectivity analyses. Results found that HUCE are associated with significant but modest decreases in connectivity of right inferior frontal gyrus (IFG)– bilateral medial frontal gyrus, right IFG – bilateral inferior parietal lobule (IPL), and right IFG – left superior frontal gyrus connectivity, as well as attentional engagement to high-calorie food and binge eating tendencies. A machine-learning method named linear support vector regression (SVR) and leave one out cross-validation (LOOCV) procedure used to examine the robustness of the brain-behavior relationship further confirm the findings. Mediation analyses suggested that right IFG – left IPL connectivity mediates the association of HUCE and binge eating tendencies. Findings suggest right IFG – left IPL connectivity may serve as a crucial neurobiological underpinning of HUCE to regulate binge eating behaviors. As such, these results contribute to a novel perspective and hypotheses in elucidating developmental neuro-mechanisms related to binge eating.

Alterations of brain activity in patients with alcohol use disorder: a resting-state fMRI study

BackgroundAlcohol use disorder (AUD) has a negative impact on one’s health and wastes a lot of societal resources since it damages one’s brain tissue. Yet the knowledge of the neural mechanisms underlying alcohol addiction still remains limited. This study aims to investigate the neural mechanisms underlying alcohol addiction by using voxel-wise binarized degree centrality (DC), weighted DC and functional connectivity (FC) methods to analyze brain network activity in individuals with AUD.MethodsThirty-three AUD patients and 29 healthy controls (HC) participated in this study. Binarized and weighted DC approach coupled with a second seed-based FC algorithm was used to assess the abnormal intrinsic hub features in AUD. We also examined the correlation between changes in functional network nodes and the severity of alcohol dependence.ResultsThirty AUD patients and 26 HC were retained after head motion correction. The spatial distribution maps of the binarized DC and weighted DC for the AUD and HC groups were roughly similar. In comparison to HC, the AUD group had decreased binarized DC and decreased weighted DC in the left precentral gyrus (PreCG) and the left inferior parietal lobule (IPL). Significantly different brain regions in the DC analysis were defined as seed points in the FC analysis. Compared with HC, changes in FC within the right inferior temporal gyrus (ITG), right middle temporal gyrus (MTG), left dorsolateral superior frontal gyrus (SFGdor), bilateral IPL, left precuneus (PCUN), left lingual gyrus (LING), right cerebellum_crus1/ITG/inferior occipital gyrus (IOG) and right superior parietal gyrus (SPG) were observed. The correlation analysis revealed that FC of right MTG-right PreCG was negatively correlated with MAST scores, and FC of right IPL-left IPL was positively correlated with ADS scores.ConclusionsAlcohol use disorder is associated with aberrant regional activities in multiple brain areas. Binarized DC, weighted DC and FC analyses may be useful biological indicators for the detection of regional brain activities in patients with AUD. Intergroup differences in FC have also been observed in AUD patients, and these variations were connected to the severity of the symptoms. The AUD patients with lower FC value of the right IPL - left IPL has a lighter dependence on alcohol. This difference in symptom severity may be a compensation for cognitive impairment, indicating a difference in pathological pathways. Future AUD research will now have a fresh path thanks to these discoveries.

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.

Cognitive impairment after sleep deprivation: The role of precuneus related connectivity on the intra-individual variability changes

ObjectiveIntra-individual variability (IIV) in cognitive performance is thought to reflect the efficiency with which attentional resources are allocated in different circumstances requiring cognitive control. IIV in cognitive performance is associated with the strength of the negative correlation between task-positive network and default mode network (DMN) activity. In this study, we investigated the impact of sleep deprivation (SD) on functional connectivity (FC) between the DMN and psychomotor vigilance task-related network (PVT-RN), and its relationship with IIV in cognitive performance. MethodsTwo analyses, network-level independent component analysis (NL-ICA) and region-level (RL)-ICA, were employed to compare the coefficient of variation (CV) of the PVT between normal sleep and SD conditions across 67 healthy participants. ResultsAfter SD, in NL-ICA, the FC between the PVT-RN and DMN was positively correlated with the CV of the PVT, as well as the changes therein, compared with normal sleep. Using a mask derived from the DMN and PVT-RN, the RL-ICA revealed that 12 edges/connections between DMN and PVT independent components were associated with the CV of the PVT, with nine of these connections involving the precuneus. ConclusionsThese findings suggest that the precuneus may play a crucial role in the interactions of various brain functions during the PVT, with the connections between the precuneus and frontoparietal and somatosensory networks being significantly altered after SD. Moreover, following SD, weakened negative FC between the precuneus and bilateral inferior parietal lobule may disrupt the balance between cognitive and executive control functions, leading to a decline in cognitive performance.

Empathy Modulates the Activity of the Sensorimotor Mirror Neuron System during Pain Observation.

The aim of this study is to analyze the brain activity patterns during the observation of painful expressions and to establish the relationship between this activity and the scores obtained on the Interpersonal Reactivity Index (IRI). The study included twenty healthy, right-handed subjects (10 women). We conducted a task-based and resting-state functional magnetic resonance imaging (fMRI) study. The task involved observing pictures displaying painful expressions. We performed a region of interest (ROI) analysis focusing on the core regions of the sensorimotor mirror neuron system (MNS). Resting-state fMRI was utilized to assess the functional connectivity of the sensorimotor MNS regions with the rest of the cortex using a seed-to-voxel approach. Additionally, we conducted a regression analysis to examine the relationship between brain activity and scores from the IRI subtests. Observing painful expressions led to increased activity in specific regions of the frontal, temporal, and parietal lobes. The largest cluster of activation was observed in the left inferior parietal lobule (IPL). However, the ROI analysis did not reveal any significant activity in the remaining core regions of the sensorimotor MNS. The regression analysis demonstrated a positive correlation between brain activity during the observation of pain and the "empathic concern" subtest scores of the IRI in both the cingulate gyri and bilateral IPL. Finally, we identified a positive relationship between the "empathic concern" subtest of the IRI and the functional connectivity (FC) of bilateral IPLs with the bilateral prefrontal cortex and the right IFG. Observing expressions of pain triggers activation in the sensorimotor MNS, and this activation is influenced by the individual's level of empathy.

Baseline markers of cortical excitation and inhibition predict response to theta burst stimulation treatment for youth depression

Theta burst stimulation (TBS), a specific form of repetitive transcranial magnetic stimulation (TMS), is a promising treatment for youth with Major Depressive Disorder (MDD) who do not respond to conventional therapies. However, given the variable response to TBS, a greater understanding of how baseline features relate to clinical response is needed to identify which patients are most likely to benefit from this treatment. In the current study, we sought to determine if baseline neurophysiology, specifically cortical excitation and/or inhibition, is associated with antidepressant response to TBS. In two independent open-label clinical trials, youth (aged 16–24 years old) with MDD underwent bilateral dorsolateral prefrontal cortex (DLPFC) TBS treatment. Clinical trial one and two consisted of 10 and 20 daily sessions of bilateral DLPFC TBS, respectively. At baseline, single-pulse TMS combined with electroencephalography was used to assess the neurophysiology of 4 cortical sites: bilateral DLPFC and inferior parietal lobule. Measures of cortical excitation and inhibition were indexed by TMS-evoked potentials (i.e., P30, N45, P60, N100, and P200). Depression severity was measured before, during and after treatment completion using the Hamilton Rating Scale for Depression—17. In both clinical trials, the baseline left DLPFC N45 and P60, which are believed to reflect inhibitory and excitatory mechanisms respectively, were predictors of clinical response. Specifically, greater (i.e., more negative) N45 and smaller P60 baseline values were associated with greater treatment response to TBS. Accordingly, cortical excitation and inhibition circuitry of the left DLPFC may have value as a TBS treatment response biomarker for youth with MDD.Clinical trial 1 registration number: NCT02472470 (June 15, 2015).Clinical trial 2 registration number: NCT03708172 (October 17, 2018).

On difference between direct-response method and strategy method in decision-making: behavioural and neural evidence in a reward-punishment game

Decision-makers may follow either the direct-response method or strategy method. While the two elicitation methods are theoretically equivalent, it is uncertain whether they lead to the same outcomes in practice. To explore this issue, we conduct an experiment based on a reward-punishment game under both methods, in which functional magnetic resonance imaging (fMRI) is used to provide neural evidence for uncovering the underlying behavioural mechanisms. The results show that both the reward and punishment rates are significantly higher under the strategy method compared to the direct-response method. We develop behavioural models to explain these differences and identify the ownership effect, strategic thinking, and counterfactual thinking as potential drivers. Comparison of neural activity between the two treatments demonstrates that during reward/no-reward decisions, the direct-response treatment accrues stronger activation in the bilateral anterior insula, indicating that decision-makers overweigh reward cost due to ownership effect, which consequently leads to reduced willingness to impose rewards. Conversely, during punishment/no-punishment decisions, the strategy treatment causes stronger activations in the bilateral anterior insula and inferior parietal lobule, implying that decision-makers perceive strong unfairness due to counterfactual thinking, which further results in more punishment decisions. Moreover, our findings reveal that strategic thinking influences decision-making during long-term interactions.

Increased brain activation and functional connectivity after working memory training in patients with ischemic stroke: an fMRI study

ObjectiveWorking memory (WM) impairment is common in patients after a stroke. WM training (WMT) has been suggested as a way to improve cognitive function. However, the neural effects following WMT in stroke patients remain largely unclear. This study aimed to explore the behavioral changes and neural effects of WMT on patients with chronic ischemic stroke.MethodsFifty first-ever ischemic stroke patients with WM deficits in the chronic stage were randomly assigned to either a 4-week WMT group or a control group. Verbal n-back, digital and spatial memory-span, Raven's standard progressive matrices, and the Stroop color-word test, as well as task-state and resting-state fMRI were assessed for all patients at baseline and after the intervention.ResultsThe WMT group showed improvements in WM, fluid intelligence, and attention after training. Additionally, the WMT group exhibited increased activation in the left middle frontal gyrus (MFG) and middle occipital gyrus after training. At baseline, all patients were impaired in their abilities to elevate activation in their WM network as a response to increasing WM load. However, in the WMT group, increased activation was observed in the left cerebellum anterior lobe, right cerebellum posterior lobe (CPL), and MFG in the 2-back vs. 1-back contrast after WMT. We also found increased functional connectivity between the left MFG and the left inferior parietal lobule (IPL), and between the bilateral IPL and the right CPL after training in the WMT group.ConclusionOur study supported that WMT potentially improved WM capacity in ischemic stroke patients during the chronic stage, and that the training effects might transfer to fluid intelligence and attention ability. Our results also demonstrated that repeated WMT potentially increased brain activation and resting-state functional connectivity within the WM network in patients with ischemic stroke. These findings provided robust evidence to support WMT as an effective intervention to enhance cognitive rehabilitation and shed light on the functional neuroplasticity mechanism of WMT on cognitive recovery after ischemic stroke.

Structural and spontaneous functional brain changes in visual and oculomotor areas identified by functional localization task in intermittent exotropia children

Intermittent exotropia (IXT) is characterizedby an intermittent outward deviation of the eyes. Yet, the neural substrates associated with IXT are not fully understood. This study investigated brain structure and spontaneous functional activity changes in children with IXT. All participants underwent detailed ophthalmological examinations and multimodal magnetic resonance imaging (MRI) scanning. During functional scanning, binocular visual stimuli were presented to subjects to determine brain areas involved in visual and oculomotor processing. Regions of interest(ROI) were subsequently selected based on functional activation to investigate brain structural and spontaneous functional differences between IXT children and healthy controls (HCs) using small volume correction (SVC). Reduced gray matter density (GMD) was found in the right frontal eye field (FEF) and bilateral inferior parietal lobe (IPL) in IXT children compared with HCs. Besides, reduced fractional amplitude of low-frequency fluctuations (fALFF) values were observed in the left lingual gyrus, right inferior occipital gyrus (IOG), bilateral IPL, and bilateral cerebellum in the IXT children compared to the HCs. IXT children with worse eye position control ability exhibited lower GMD and fALFF values in these areas. Finally, resting state functional connectivity (RSFC) was reduced in frontoparietal oculomotor processing areas in IXT children compared to HCs. In addition, increased cortical thickness was found in the right visual areas and bilateral IPL. These results showed that IXT-related structural and functional brain abnormalities occurred in childhood and may be related to underlying neuropathological mechanisms.

Functional changes in the salience network of patients with amnesic mild cognitive impairment before and after repetitive transcranial magnetic stimulation.

Amnestic mild cognitive impairment (aMCI) is considered to be the prodromal stage of Alzheimer's disease (AD). The precuneus (PCUN) may be an imaging marker for monitoring the progression of AD. Meanwhile, cognitive impairment in AD patients is closely related to functional connectivity (FC) changes in the salience network (SN). We hypothesize that there are specific neuroimaging biomarkers in the SN and that FC changes in aMCI patients after repetitive transcranial magnetic stimulation (rTMS) intervention are associated with cognitive function. The purpose of this study was to first investigate the pattern of functional changes in aMCI patients and healthy controls (HCs) and then compare the functional changes in aMCI patients before and after rTMS targeting to PCUN and its correlation with cognitive function. Thirty-six HCs and 61 aMCIs were recruited for our study. Eleven people in the aMCI group received rTMS intervention 5 days a week for 4 weeks. Using the right anterior insula as the seed-of-interest, we first compared FC changes in HC and aMCI patients and then compared cognitive function in aMCI patients before and after rTMS. The above is the functional connection analysis of seed-to-voxel. Moreover, we investigated the FC changes in aMCI patients after rTMS intervention and its correlation with cognitive function. Compared with HC, the aMCI group showed altered FC in bilateral parahippocampal gyrus, bilateral inferior parietal lobule, left middle frontal gyrus, and left middle temporal gyrus. Moreover, rTMS at PCUN improved the cognitive function of aMCI patients, which was related to the altered FC in posterior cerebellar lobes (CPL). Our findings suggest that rTMS targeting PCUN is a promising, noninvasive approach to ameliorating cognitive dysfunction in aMCI patients, and that this cognitive improvement is accompanied by brain connectivity modulation.

Abnormal cerebral metabolism and metabolic connectivity in individuals with heroin dependence: an integrated resting-state PET/fMRI study in large-scale networks.

Increasing evidence suggests that heroin addiction may be related to the dysfunction among the triple brain network (default mode network [DMN], salience network [SN] and executive control network [ECN]). However, the characteristics of glucose metabolism and metabolic connectivity among core regions of the triple brain network remain unknown. Therefore, we hypothesized that individuals with heroin dependence would show abnormal glucose metabolism and accompanied abnormal metabolic connectivity within the triple brain network. Individuals with heroin dependence and healthy controls matched for age and sex underwent integrated positron emission tomography/magnetic resonance imaging (PET/MRI). Differences in glucose metabolism and metabolic connectivity among the DMN, SN and ECN were analyzed based on 18F-fluorodeoxyglucose PET and resting-state fMRI data. We included 36 individuals with heroin dependence and 30 matched healthy controls in our study. The heroin dependence group showed a significant reduction of glucose metabolism in the bilateral anterior insula (AI) and inferior parietal lobule (IPL), and a significantly decreased metabolic connectivity between the right AI and the left dorsolateral prefrontal cortex (DLPFC). The daily dose of methadone was negatively correlated with glucose metabolism of the right AI and right IPL. The results revealed the glucose metabolism alterations and metabolic connectivity only within the triple brain network in individuals with heroin dependence; additional brain networks should be investigated in future studies. Although methadone is an opioid with a similar neurophysiological mechanism as heroin, the specific chronic effects of methadone on cerebral metabolism and metabolic connectivity should also be investigated in future studies. Our findings suggest that long-term opioid use might, to some extent, be associated with reduced synergistic ability between the SN and ECN, which may be associated with the dysfunction of cognitive control. In particular, the right AI, which showed hypometabolism and related reduction in SN-ECN metabolic connectivity, should receive increasing attention in future studies.

Cortical responses correlate with speech performance in pre-lingually deaf cochlear implant children.

Cochlear implantation is currently the most successful intervention for severe-to-profound sensorineural hearing loss, particularly in deaf infants and children. Nonetheless, there remains a significant degree of variability in the outcomes of CI post-implantation. The purpose of this study was to understand the cortical correlates of the variability in speech outcomes with a cochlear implant in pre-lingually deaf children using functional near-infrared spectroscopy (fNIRS), an emerging brain-imaging technique. In this experiment, cortical activities when processing visual speech and two levels of auditory speech, including auditory speech in quiet and in noise with signal-to-noise ratios of 10 dB, were examined in 38 CI recipients with pre-lingual deafness and 36 normally hearing children whose age and sex matched CI users. The HOPE corpus (a corpus of Mandarin sentences) was used to generate speech stimuli. The regions of interest (ROIs) for the fNIRS measurements were fronto-temporal-parietal networks involved in language processing, including bilateral superior temporal gyrus, left inferior frontal gyrus, and bilateral inferior parietal lobes. The fNIRS results confirmed and extended findings previously reported in the neuroimaging literature. Firstly, cortical responses of superior temporal gyrus to both auditory and visual speech in CI users were directly correlated to auditory speech perception scores, with the strongest positive association between the levels of cross-modal reorganization and CI outcome. Secondly, compared to NH controls, CI users, particularly those with good speech perception, showed larger cortical activation in the left inferior frontal gyrus in response to all speech stimuli used in the experiment. In conclusion, cross-modal activation to visual speech in the auditory cortex of pre-lingually deaf CI children may be at least one of the neural bases of highly variable CI performance due to its beneficial effects for speech understanding, thus supporting the prediction and assessment of CI outcomes in clinic. Additionally, cortical activation of the left inferior frontal gyrus may be a cortical marker for effortful listening.

Distinct regional and hemispheric tau distributions in Primary Progressive Aphasia with neuropathologic Progressive Supranuclear Palsy: A stereological study

AbstractBackgroundPrimary Progressive Aphasia (PPA) is a dementia syndrome characterized by isolated and progressive impairment of language and focal atrophy of left‐hemispheric cortical regions. PPA presents with various underlying FTLD‐tauopathies such as Pick’s disease (PiD), corticobasal degeneration (CBD), and progressive supranuclear palsy (PSP). This study investigated clinicopathologic concordance between the aphasic phenotype of PPA and regional distributions of PSP markers quantified in language‐related cortical areas and the dentate gyrus (DG) of the hippocampus—an area of interest due to intact memory exhibited in PPA. Another goal was to compare regional distributions of tau‐positive markers in PSP compared to CBD and PiD to identify differential susceptibility patterns across FTLD‐tauopathies.MethodParaffin‐embedded sections were stained immunohistochemically with AT‐8 to visualize neuronal tau inclusions and astrocytes containing phosphorylated tau in 8 right‐handed cases with PPA and autopsy‐confirmed PSP. Modified unbiased stereology was performed in bilateral middle frontal gyrus (MFG) and inferior parietal lobule (IPL), and left DG. A secondary analysis compared distributions of tau markers in cases with PiD (N = 6; tau‐positive inclusions) and CBD (N = 4; tau‐positive inclusions + astrocytic plaques). One‐way ANOVAs and students’ t‐tests were used to analyze distributions.ResultWithin the PSP group, there was significant left‐sided asymmetric predominance of tau‐positive neuronal inclusions and astrocytic tau in cortical areas; left MFG showed over double the total marker density vs right (3,490 vs 1,549 counts/mm3, respectively; p<0.05). In PSP, there was significantly less tau‐positive inclusions and astrocytes in the DG relative to cortical regions, where the ratio of left‐sided dentate‐to‐cortical inclusions was ∼1:2. This was remarkably lower than dentate‐to‐cortical ratios of ∼2:1 in CBD and ∼3:1 in PiD (p<0.01). Finally, PSP cases showed significantly greater astrocytic tau in cortical regions compared to CBD, by ∼100 fold in the left hemisphere (p<0.01).ConclusionFindings from this stereological study of PPA with FTLD‐PSP show leftward cortical predominance of pathology concordant with the salience of the aphasic phenotype. Dentate predominance of pathology in PPA due to FTLD‐tau remains a mystery. The relative distribution of dentate‐to‐cortical tau pathology is different across FTLD‐tau species, offering insights into the selective vulnerability of distinct neuronal populations in neurodegenerative dementias.

Brain responses to energy intake and its association with cognition in Alzheimer’s Disease

AbstractBackgroundTo evaluate the brain response to energy intake using cerebral blood flow(CBF) in Alzheimer’s disease (AD), mild cognitive impairment (MCI) and healthy controls (HC) and its relationship with cognition.MethodA self‐comparison design was used to test the effects of energy intake on brain activity in participants with AD (n = 30), MCI participants (n = 32), and HC (n = 30) and its relationship with cognitive function. Brain perfusion was measured using arterial spin labeling (ASL) functional brain imaging. Participants arrived at the site in the morning and underwent the ASL‐MRI with at least 10 hours fasting overnight. Then the second ASL‐MRI at 30 minutes after eating a standard breakfast was performed. Energy response ΔCBF was computed by subtracting the fasting CBF from the postprandial CBF obtained from ASL‐MRI. Whole brain grey matter voxel‐wise paired T test and linear regression analyses were used for statistical analysis.ResultAD and MCI group had different energy response ΔCBF pattern with HC group. In AD group, energy intake induced a significantly decreased CBF in temporal lobe including lateral inferior and superior temporal gyrus, right superior temporal gyrus, parietal lobe including bilateral superior and inferior parietal lobe, postcentral gyrus and precuneus, most of occipital lobe and frontal lobe including right rolandic operculum, right precentral gyrus and left middle frontal gyrus. (q < 0.05, false discovery rate corrected). MCI had similar energy intake response pattern with AD. HC group had no significantly changed CBF response to energy intake. Energy response ΔCBF in the vicinity of the superior temporal gyrus showed significant negative correlation with Minimum Mental State Examination (MMSE) in all AD, MCI and HC groups.ConclusionThe different energy response ΔCBF pattern may help to characterize the energy disorder in AD and may indicate the different brain energy rescue effect in the three groups. Energy response ΔCBF in the superior temporal gyrus is an indicator of cognitive function in AD.

Neural correlates of autobiographical memory retrieval: An SDM neuroimaging meta-analysis

Autobiographical memory (AM) is a type of episodic memory that involves the recollection and re-experiencing of personal life events. AM retrieval is a complex process requiring the coordination of multiple memory processes across the brain. Important questions remain regarding the degree to which specific brain regions are consistently recruited during AM retrieval and the influence of methodological factors such as type of AM retrieval task and control task. Neuroimaging meta-analyses can summarize the brain regions associated with AM retrieval, addressing these questions by revealing consistent findings across multiple studies. We used a coordinate-based neuroimaging meta-analysis method, seed-based d mapping (SDM), to assess the largest set of neuroimaging studies of AM retrieval to date. An important advantage of SDM over other methods is that it factors in the effect sizes of the activation coordinates from studies, yielding a more representative summary of activations. Studies were selected if they elicited AM retrieval in the scanner, contrasted AM retrieval with a matched control task, and used univariate whole-brain analyses, yielding a set of 50 papers with 963 participants and 891 foci. The findings confirmed the recruitment of many previously identified core AM retrieval regions including the prefrontal cortex (PFC), hippocampus and parahippocampal cortex, retrosplenial cortex and posterior cingulate, and angular gyrus, and revealed additional regions, including bilateral inferior parietal lobule and greater activation extent through the PFC, including lateral PFC activation. Results were robust across different types of AM retrieval tasks (previously rehearsed cues vs. novel cues), and robust across different control tasks (visual/attention vs. semantic retrieval). To maximize the utility of the meta-analysis, all results image files are available online. In summary, the current meta-analysis provides an updated and more representative characterization of the neural correlates of autobiographical memory retrieval and how these neural correlates are affected by important experimental factors.

Dysfunction of default mode network characterizes generalized anxiety disorder relative to social anxiety disorder and post-traumatic stress disorder

BackgroundThe perseverative cognition of generalized anxiety disorder (GAD) is distinctive compared to other anxiety disorders. However, the disease-specific and shared neuropathophysiological mechanisms of GAD remain unclear. MethodsWe recruited medication-free patients of GAD (N = 33), social anxiety disorder (SAD; N = 36), post-traumatic stress disorder (PTSD; N = 59), and healthy controls (HC; N = 50). All subjects underwent clinical assessments and resting-state functional magnetic resonance imaging. We compared both the amplitude low-frequency fluctuation (ALFF) and seed-based functional connectivity across the whole brain, using the significantly different regions from the ALFF analyses as seed regions, followed by post-hoc tests. ResultsWe found that ALFF of the left angular gyrus (AG), left inferior parietal lobule (IPL), left precentral gyrus, left middle temporal gyrus, and left cerebellum were higher in GAD compared with SAD, PTSD and HC. This trend was further corroborated by the higher functional connectivity between left AG and bilateral IPL, left inferior temporal gyrus, and left medial prefrontal cortex (mPFC) in GAD. In addition, GAD and SAD both showed abnormally higher left AG-right insula connectivity. Significant correlations were found between anxiety symptom severity and the left AG regional activity and left AG-left mPFC connectivity. LimitationsWe did not compare the differences in neuroimaging between GAD and other anxiety disorders, such as panic disorder. ConclusionsThe default mode network dysfunction may underlie the distinctive perseverative thoughts of GAD relative to other anxiety disorders, and left AG-right insula connectivity may reflect somatic anxiety of anxiety disorder spectrum.

Neural basis of cooperation in the Prisoner's Dilemma in a loss context

Using functional magnetic resonance imaging (fMRI) technology, we conducted an experiment to explore the effects of gain and loss contexts on cooperation and its brain activation patterns in the Prisoner's Dilemma game. The results showed that even in a loss context, participants still chose cooperation in nearly half of the experiment trials, but the cooperation rate was higher in a gain context. The results of fMRI showed that the right ventromedial prefrontal cortex, right dorsomedial prefrontal cortex, right temporoparietal junction, and right precuneus were activated more in the decision process of making a cooperative rather than a defection choice, and also that the activation of the bilateral precuneus and bilateral inferior parietal lobule induced by a cooperative choice was greater in a loss context than in a gain context. Thus, compared with when they were making a defection decision, in the process of making a cooperative decision, participants might reason and process more on the psychological activities of others, especially in a loss context.