The Relationship of Four Brain Regions to an Information-Processing Model of Numerical Inductive Reasoning Process: An fMRI Study

The present study relates a four-stage information-processing model of inductive reasoning to four brain regions. We assume that there is a fusiform gyrus region-of-interest (ROI) where a stimulus is visually recognized, a DLPFC ROI where an underlying rule is identified, a caudate ROI where a rule is applied, and a motor ROI where hand movements are programmed during inductive reasoning process. Then, an fMRI experiment was performed to articulate the roles of these four regions. The present study is a 2 (task: rule induction vs. rule application) × 2 (period length: simple vs. complex) × 2 (priming effect: prime vs. target) design. As predicted, both the fusiform gyrus ROI and the motor ROI showed no effects of task, period length, and priming effect, and respectively reflected encoding of stimuli and button-pressing response. The DLPFC ROI responded to task and period length, and was confirmed to play a crucial role in rule identification. The caudate showed no effect of task and responded to period length and priming effect, and was verified to be responsible for rule application. The exploratory analysis also demonstrated our assumptions. Thus, the main stream of information-processing in inductive reasoning process can be described by using the four ROIs

Precuneus Dysfunction in Parkinson’s Disease With Mild Cognitive Impairment

Background: Mild cognitive impairment (MCI) frequently occurs in Parkinson’s disease (PD). Neurovascular changes interact with neurodegenerative processes in PD. However, the deficits of cerebral blood flow (CBF) perfusion and the associated functional connectivity (FC) in PD patients with MCI (PD-MCI) remain unclear.Purpose: This study aimed to explore the specific neurovascular perfusion alterations in PD-MCI compared to PD with normal cognition (PD-NC) and healthy controls (HCs), and to further examine the resultant whole brain FC changes in the abnormal perfusion regions.Methods: Relative CBF (rCBF) was calculated using arterial spin labeling (ASL) in 54 patients with PD (27 patients with PD-NC and 27 patients with PD-MCI) and 25 HCs matched for age and gender ratio, who also underwent the structural MRI, resting-state functional MRI (rs-fMRI) and neuropsychological examinations. The gray matter (GM) changes in PD patients were analyzed using voxel-based morphometry (VBM). The alterations in rCBF perfusion and FC among groups were then analyzed respectively. Additionally, correlations between these alterations and neuropsychological performances were further examined.Results: Compared to HC, left caudate atrophy was detected in patients with PD. In comparison to both PD-NC and HC, patients with PD-MCI specifically exhibited hypoperfusion in the parietal memory network (PMN) in the precuneus (PCu) and decreased PCu-FC in the right striatum. Moreover, PCu perfusion and PCu-FC strengths in the right striatum were positively associated with memory performance in PD-MCI.Conclusions: These findings suggest that the posterior PMN dysfunction underlies memory deficits in PD-MCI

Activity in the fronto-parietal network indicates numerical inductive reasoning beyond calculation:An fMRI study combined with a cognitive model

Numerical inductive reasoning refers to the process of identifying and extrapolating the rule involved in numeric materials. It is associated with calculation, and shares the common activation of the fronto-parietal regions with calculation, which suggests that numerical inductive reasoning may correspond to a general calculation process. However, compared with calculation, rule identification is critical and unique to reasoning. Previous studies have established the central role of the fronto-parietal network for relational integration during rule identification in numerical inductive reasoning. The current question of interest is whether numerical inductive reasoning exclusively corresponds to calculation or operates beyond calculation, and whether it is possible to distinguish between them based on the activity pattern in the fronto-parietal network. To directly address this issue, three types of problems were created: numerical inductive reasoning, calculation, and perceptual judgment. Our results showed that the fronto-parietal network was more active in numerical inductive reasoning which requires more exchanges between intermediate representations and long-term declarative knowledge during rule identification. These results survived even after controlling for the covariates of response time and error rate. A computational cognitive model was developed using the cognitive architecture ACT-R to account for the behavioral results and brain activity in the fronto-parietal network.</p

Altered Functional Connectivity of the Basal Nucleus of Meynert in Mild Cognitive Impairment: A Resting-State fMRI Study

Background: Cholinergic dysfunction plays an important role in mild cognitive impairment (MCI). The basal nucleus of Meynert (BNM) provides the main source of cortical cholinergic innervation. Previous studies have characterized structural changes of the cholinergic basal forebrain in individuals at risk of developing Alzheimer’s disease (AD). However, whether and how functional connectivity of the BNM (BNM-FC) is altered in MCI remains unknown.Objective: The aim of this study was to identify alterations in BNM-FC in individuals with MCI as compared to healthy controls (HCs), and to examine the relationship between these alterations with neuropsychological measures in individuals with MCI.Method: One-hundred-and-one MCI patients and 103 HCs underwent resting-state functional magnetic resonance imaging (rs-fMRI). Imaging data were processed with SPM8 and CONN software. BNM-FC was examined via correlation in low frequency fMRI signal fluctuations between the BNM and all other brain voxels. Group differences were examined with a covariance analysis with age, gender, education level, mean framewise displacement (FD) and global correlation (GCOR) as nuisance covariates. Pearson’s correlation was conducted to evaluate the relationship between the BNM-FC and clinical assessments.Result: Compared with HCs, individuals with MCI showed significantly decreased BNM-FC in the left insula extending into claustrum (insula/claustrum). Furthermore, greater decrease in BNM-FC with insula/claustrum was associated with more severe impairment in immediate recall during Auditory Verbal Learning Test (AVLT) in MCI patients.Conclusion: MCI is associated with changes in BNM-FC to the insula/claustrum in relation to cognitive impairments. These new findings may advance research of the cholinergic bases of cognitive dysfunction during healthy aging and in individuals at risk of developing AD

Disrupted Functional Connectivity of Cornu Ammonis Subregions in Amnestic Mild Cognitive Impairment: A Longitudinal Resting-State fMRI Study

Background: The cornu ammonis (CA), as part of the hippocampal formation, represents a primary target region of neural degeneration in amnestic mild cognitive impairment (aMCI). Previous studies have revealed subtle structural deficits of the CA subregions (CA1-CA3, bilateral) in aMCI; however, it is not clear how the network function is impacted by aMCI. The present study examined longitudinal changes in resting state functional connectivity (FC) of each CA subregion and how these changes relate to neuropsychological profiles in aMCI.Methods: Twenty aMCI and 20 healthy control (HC) participants underwent longitudinal cognitive assessment and resting state functional MRI scans at baseline and 15 months afterward. Imaging data were processed with published routines in SPM8 and CONN software. Two-way analysis of covariance was performed with covariates of age, gender, education level, follow up interval, gray matter volume, mean FD, as well as global correlation (GCOR). Pearson’s correlation was conducted to evaluate the relationship between the longitudinal changes in CA subregional FC and neuropsychological performance in aMCI subjects.Results: Resting state FC between the right CA1 and right middle temporal gyrus (MTG) as well as between the left CA2 and bilateral cuneal cortex (CC) were decreased in aMCI subjects as compared to HC. Longitudinal decrease in FC between the right CA1 and right MTG was correlated with reduced capacity of episodic memory in aMCI subjects.Conclusion: The current findings suggest functional alterations in the CA subregions. CA1 connectivity with the middle temporal cortex may represent an important neural marker of memory dysfunction in aMCI

Aberrant Brain Regional Homogeneity and Functional Connectivity of Entorhinal Cortex in Vascular Mild Cognitive Impairment: A Resting-State Functional MRI Study

The aim of this study was to investigate changes in regional homogeneity (ReHo) and the functional connectivity of the entorhinal cortex (EC) in vascular mild cognitive impairment (VaMCI) and to evaluate the relationships between such changes and neuropsychological measures in VaMCI individuals. In all, 31 patients with VaMCI and 32 normal controls (NCs) underwent rs-fMRI. Differences in whole-brain ReHo and seed-based bilateral EC functional connectivity (EC-FC) were determined. Pearson's correlation was used to evaluate the relationships between regions with significant group differences and different neuropsychological measures. Vascular mild cognitive impairment (VaMCI) patients had lower scores in Mini-mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) and higher ones in Activity of Daily Living (ADL) (p &lt; 0.05). Vascular mild cognitive impairment (VaMCI) individuals had significantly lower ReHo in the left cerebellum and right lentiform nucleus than NCs (P &lt; 0.05, TFCE FWE correction). Vascular mild cognitive impairment (VaMCI) subjects showed significant decreases in the FC of the right EC in the right inferior frontal gyrus, right middle frontal gyrus, bilateral pre-central gyrus, and right post-central/superior parietal lobules (P &lt; 0.05, TFCE FWE correction). Significant positive correlations were found between ReHo and MoCA scores for the right lentiform nucleus (r = 0.37, P &lt; 0.05). The right post-central/superior parietal lobules showed a significant positive correlation between right EC-FC and MoCA scores (r = 0.37, P &lt; 0.05). Patterns in ReHo and EC-FC changes in VaMCI patients and their correlations with neuropsychological measures may be a pathophysiological foundation of cognitive impairment, which may aid the early diagnosis of VaMCI

Abnormal Spontaneous Brain Activity in Early Parkinson’s Disease With Mild Cognitive Impairment: A Resting-State fMRI Study

Mild cognitive impairment (MCI) is a common symptom at the baseline of early Parkinson’s disease (PD) diagnosis, but the neural mechanism is unclear. To address the issue, the present study employed resting-state functional magnetic resonance imaging data of 19 drug-naïve PD patients with normal cognition (PD-NC), 10 PD patients with MCI (PD-MCI) and 13 age- and gender-matched healthy controls (HC) from the Parkinson’s progression markers initiative (PPMI) (http://www.ppmi-info.org/), and examined abnormal spontaneous brain activities in the PD-MCI. The pattern of spontaneous brain activity was measured by examining the amplitude of low-frequency fluctuations (ALFF) of blood oxygen level dependent signal. Voxel-wise one-way analysis of covariance and post hoc analyses of ALFF were performed under non-parametric permutation tests in a general linear model among the three groups, with age, gender and data center as additional covariates. Statistical significances in the post hoc analysis were corrected by a small volume correction with a cluster-level threshold of p &lt; 0.05 (n = 10000 permutations, FWE-corrected). Correlations of clinical and neuropsychological assessments [i.e., Unified Parkinson’s Disease Rating Scale (UPDRS) total score, Montreal Cognitive Assessment (MoCA) and cognitive domains] with the regional ALFF were performed in the PD-MCI group. Compared with the HC, both PD groups exhibited reduced ALFF in the occipital area (Calcarine_R/Cuneus_R). Specially, the PD-MCI group additionally exhibited increased ALFF in the opercular part of right inferior frontal gyrus (Frontal_Inf_Oper_R). Comparing with the PD-NC, the PD-MCI group exhibited significantly higher ALFF in the Frontal_Inf_Oper_R and left fusiform gyus (ps &lt; 0.05). The correlation analysis revealed that the ALFF in the Frontal_Inf_Oper_R was positively correlated with the UPDRS total score (p &lt; 0.05), but marginally negatively correlated with the MoCA score. For cognitive domains, the ALFF in the region also showed a significantly negative correlation with the score of SF test (p &lt; 0.01) and a marginally negative correlation with the score of Symbol-Digit Modalities Test. Together, we concluded hyperactivity in the right inferior frontal gyrus in early PD with MCI, suggesting a compensatory recruitment in response to cognitive decline, which may shed light on thought of dementia progression and potentially comprehensive treatment in PD

Functional Disconnection and Compensation in Mild Cognitive Impairment: Evidence from DLPFC Connectivity Using Resting-State fMRI

The known regional abnormality of the dorsolateral prefrontal cortex (DLPFC) and its role in various neural circuits in mild cognitive impairment (MCI) has given prominence to its importance in studies on the disconnection associated with MCI. The purpose of the current study was to examine the DLPFC functional connectivity patterns during rest in MCI patients and the impact of regional grey matter (GM) atrophy on the functional results. Structural and functional MRI data were collected from 14 MCI patients and 14 age, gender-matched healthy controls. We found that both the bilateral DLPFC showed reduced functional connectivity with the inferior parietal lobule (IPL), superior/medial frontal gyrus and sub-cortical regions (e.g., thalamus, putamen) in MCI patients when compared with healthy controls. Moreover, the DLPFC connectivity with the IPL and thalamus significantly correlated with the cognitive performance of patients as measured by mini-mental state examination (MMSE), clock drawing test (CDT), and California verbal learning test (CVLT) scores. When taking GM atrophy as covariates, these results were approximately consistent with those without correction, although there may be a decrease in the statistical power. These results suggest that the DLPFC disconnections may be the substrates of cognitive impairments in MCI patients. In addition, we also found enhanced functional connectivity between the left DLPFC and the right prefrontal cortex in MCI patients. This is consistent with previous findings of MCI-related increased activation during cognitive tasks, and may represent a compensatory mechanism in MCI patients. Together, the present study demonstrated the coexistence of functional disconnection and compensation in MCI patients using DLPFC functional connectivity analysis, and thus might provide insights into biological mechanism of the disease