Abnormal EEG microstates in Alzheimer's disease: predictors of ß-amyloid deposition degree and disease classification.

Electroencephalography (EEG) microstates are used to study cognitive processes and brain disease-related changes. However, dysfunctional patterns of microstate dynamics in Alzheimer's disease (AD) remain uncertain. To investigate microstate changes in AD using EEG and assess their association with cognitive function and pathological changes in cerebrospinal fluid (CSF). We enrolled 56 patients with AD and 38 age- and sex-matched healthy controls (HC). All participants underwent various neuropsychological assessments and resting-state EEG recordings. Patients with AD also underwent CSF examinations to assess biomarkers related to the disease. Stepwise regression was used to analyze the relationship between changes in microstate patterns and CSF biomarkers. Receiver operating characteristics analysis was used to assess the potential of these microstate patterns as diagnostic predictors for AD. Compared with HC, patients with AD exhibited longer durations of microstates C and D, along with a decreased occurrence of microstate B. These microstate pattern changes were associated with Stroop Color Word Test and Activities of Daily Living scale scores (all P < 0.05). Mean duration, occurrences of microstate B, and mean occurrence were correlated with CSF Aß 1-42 levels, while duration of microstate C was correlated with CSF Aß 1-40 levels in AD (all P < 0.05). EEG microstates are used to predict AD classification with moderate accuracy. Changes in EEG microstate patterns in patients with AD correlate with cognition and disease severity, relate to Aß deposition, and may be useful predictors for disease classification.

Effects of a periodic intermittent theta burst stimulation in Alzheimer's disease.

Background: Previous studies have demonstrated that excitatory repetitive transcranial magnetic stimulation (rTMS) can improve the cognitive function of patients with Alzheimer's disease (AD). Intermittent theta burst stimulation (iTBS) is a novel excitatory rTMS protocol for brain activity stimulation with the ability to induce long-term potentiation-like plasticity and represents a promising treatment for AD. However, the long-term effects of iTBS on cognitive decline and brain structure in patients with AD are unknown. Aims: We aimed to explore whether repeating accelerated iTBS every three months could slow down the cognitive decline in patients with AD. Methods: In this randomised, assessor-blinded, controlled trial, iTBS was administered to the left dorsolateral prefrontal cortex (DLPFC) of 42 patients with AD for 14 days every 13 weeks. Measurements included the Montreal Cognitive Assessment (MoCA), a comprehensive neuropsychological battery, and the grey matter volume (GMV) of the hippocampus. Patients were evaluated at baseline and after follow-up. The longitudinal pipeline of the Computational Anatomy Toolbox for SPM was used to detect significant treatment-related changes over time. Results: The iTBS group maintained MoCA scores relative to the control group (t=3.26, p=0.013) and reduced hippocampal atrophy, which was significantly correlated with global degeneration scale changes. The baseline Mini-Mental State Examination (MMSE) score, apolipoprotein E genotype and Clinical Dementia Rating were indicative of MoCA scores at follow-up. Moreover, the GMV of the left (t=0.08, p=0.996) and right (t=0.19, p=0.977) hippocampus were maintained in the active group but significantly declined in the control group (left: t=4.13, p<0.001; right: t=5.31, p<0.001). GMV change in the left (r=0.35, p=0.023) and right (r=0.36, p=0.021) hippocampus across the intervention positively correlated with MoCA changes; left hippocampal GMV change was negatively correlated with global degeneration scale (r=-0.32, p=0.041) changes. Conclusions: DLPFC-iTBS may be a feasible and easy-to-implement non-pharmacological intervention to slow down the progressive decline of overall cognition and quality of life in patients with AD, providing a new AD treatment option. Trial registration number: NCT04754152.

High-Definition Transcranial Direct Current Stimulation Improves Decision-Making Ability: A Study Based on EEG.

High-definition transcranial direct current stimulation (HD-tDCS) has been shown to modulate decision-making; however, the neurophysiological mechanisms underlying this effect remain unclear. To further explore the neurophysiological processes of decision-making modulated by HD-tDCS, health participants underwent ten anodal (n = 16)/sham (n = 17) HD-tDCS sessions targeting the left DLPFC. Iowa gambling task was performed simultaneously with electroencephalography (EEG) before and after HD-tDCS. Iowa gambling task performance, the P300 amplitude, and the power of theta oscillation as an index of decision-making were compared. Behavioral changes were found that showed anodal HD-tDCS could improve the decision-making function, in which participants could make more advantageous choices. The electrophysiological results showed that the P300 amplitude significantly increased in CZ, CPZ electrode placement site and theta oscillation power significantly activated in FCZ, CZ electrode placement site after anodal HD-tDCS. Significant positive correlations were observed between the changes in the percent use of negative feedback and the changes in theta oscillation power before and after anodal HD-tDCS. This study showed that HD-tDCS is a promising technology in improving decision-making and theta oscillation induced by may be a predictor of improved decision-making.

White Matter Changes as an Independent Predictor of Alzheimer's Disease.

BACKGROUND: Abnormalities in white matter (WM) may be a crucial physiologic feature of Alzheimer's disease (AD). However, neuroimaging's ability to visualize the underlying functional degradation of the WM region in AD is unclear. OBJECTIVE: This study aimed to explore the differences in amplitude of low-frequency fluctuation (ALFF) and fractional ALFF (fALFF) in the WM region of patients with AD and healthy controls (HC) and to investigate further whether these values can provide supplementary information for diagnosing AD. METHODS: Forty-eight patients with AD and 46 age-matched HC were enrolled and underwent resting-state functional magnetic resonance imaging and a neuropsychological battery assessment. We analyzed the differences in WM activity between the two groups and further explored the correlation between WM activity in the different regions and cognitive function in the AD group. Finally, a machine learning algorithm was adopted to construct a classifier in detecting the clinical classification ability of the values of ALFF/ALFF in the WM. RESULTS: Compared with HCs, patients with AD had lower WM activity in the right anterior thalamic radiation, left frontal aslant tract, and left forceps minor, which are all positively related to global cognitive function, memory, and attention function (all p < 0.05). Based on the combined WM ALFF and fALFF characteristics in the different regions, individuals not previously assessed were classified with moderate accuracy (75%), sensitivity (71%), specificity (79%), and area under the receiver operating characteristic curve (85%). CONCLUSION: Our results suggest that WM activity is reduced in AD and can be used for disease classification.

The correlation of retinal neurodegeneration and brain degeneration in patients with Alzheimer's disease using optical coherence tomography angiography and MRI.

Introduction: Pathological changes in Alzheimer's disease can cause retina and optic nerve degeneration. The retinal changes are correlated with cognitive function. This study aimed to explore the relationship of retinal differences with neuroimaging in patients with Alzheimer's disease, analyze the association of cognitive function with retinal structure and vascular density, and identify potential additional biomarkers for early diagnosis of Alzheimer's disease. Method: We performed magnetic resonance imaging (MRI) scans and neuropsychological assessments in 28 patients with mild Alzheimer's disease and 28 healthy controls. Retinal structure and vascular density were evaluated by optical coherence tomography angiography (OCTA). Furthermore, we analyzed the correlation between neuroimaging and OCTA parameters in patients with mild Alzheimer's disease with adjustment for age, gender, years of education, and hypertension. Results: In patients with mild Alzheimer's disease, OCTA-detected retinal parameters were not significantly correlated with MRI-detected neuroimaging parameters after Bonferroni correction for multiple testing. Under multivariable analysis controlled for age, gender, years of education, and hypertension, the S-Hemi (0-3) sector of macular thickness was significantly associated with Mini-cog (ß = 0.583, P = 0.002) with Bonferroni-corrected threshold at P < 0.003. Conclusion: Our findings suggested decreased macular thickness might be associated with cognitive function in mild AD patients. However, the differences in retinal parameters didn't correspond to MRI-detected parameters in this study. Whether OCTA can be used as a new detection method mirroring MRI for evaluating the effect of neuronal degeneration in patients with mild Alzheimer's disease still needs to be investigated by more rigorous and larger studies in the future.

Optimized Magnetic Stimulation Induced Hypoconnectivity Within the Executive Control Network Yields Cognition Improvements in Alzheimer's Patients.

Alzheimer's disease (AD) is a severe neurodegenerative disease, which mainly manifests as memory and progressive cognitive impairment. At present, there is no method to prevent the progression of AD or cure it, and effective intervention methods are urgently needed. Network-targeted intermittent theta burst stimulation (iTBS) may be effective in alleviating the cognitive symptoms of patients with mild AD. The abnormal function of the dorsolateral prefrontal cortex (DLPFC) within executive control network (ECN) may be the pathogenesis of AD. Here, we verify the abnormality of the ECN in the native AD data set, and build the relevant brain network. In addition, we also recruited AD patients to verify the clinical effects of DLPFC-targeted intervention, and explor the neuro-mechanism. Sixty clinically diagnosed AD patients and 62 normal controls were recruited to explore the ECN abnormalities. In addition, the researchers recruited 20 AD patients to explore the efficacy of 14-session iTBS treatments for targeted DLPFC interventions. Functional magnetic resonance imaging and neuropsychological assessment of resting state were performed before and after the intervention. Calculate the changes in the functional connectivity of related brain regions in the ECN, as well as the correlation between the baseline functional connectivity and the clinical scoring scale, to clarify the mechanism of the response of iTBS treatment to treatment. Our results showed that compared with normal control samples, the brain function connection between the left DLPFC and the left IPL within the ECN of AD patients was significantly enhanced (t = 2.687, p = 0.008, FDR-corrected p = 0.045). And we found that iTBS stimulation significantly reduced the functional magnetic resonance imaging signal between the left DLPFC and the left IPL in the ECN (t = 4.271, p < 0.001, FDR-corrected p = 0.006), and it was related to the improvement of the patient's clinical symptoms (r = -0.470, p = 0.042). This work provides new insights for targeted brain area interventions. By targeted adjusting the functional connection of ECN to improve the clinical symptoms and cognitive function of AD patients.

Intermittent theta burst stimulation improved visual-spatial working memory in treatment-resistant schizophrenia: A pilot study.

BACKGROUND: Visual-spatial working memory (vsWM) impairment in treatment-resistant schizophrenia (TRS) currently has no satisfactory treatment. Our study aimed to improve vsWM function in TRS through intermittent theta burst stimulation (iTBS) using neuronavigation equipment to target the left dorsolateral prefrontal cortex. METHOD: TRS patients (n = 59) were randomly allocated to receive iTBS (n = 33) or a sham treatment (n = 26) over 2 weeks. The participants including TRS patients and healthy controls (HCs) performed the vsWM n-back task, and TRS patients' neuroimaging data were acquired before and after treatment. All patients also underwent a battery of symptom measures to assess the severity of illness. The main outcome measure was the accuracy (ACC) of n-back target responses, particularly 3-back ACC. RESULTS: The iTBS group showed considerable improvement in n-back ACC compared to the sham group, especially 3-back ACC. After iTBS, performance on the n-back task was comparable to that of HCs. The interaction (group × time) results showed increased fractional amplitude of low frequency fluctuations (fALFF) in the right occipital areas and decreased fALFF in the right precuneus. However, there was a negative correlation between the 3-back ACC and improved clinical symptoms scores. Improvements in 3-back ACC were positively correlated with activity in the right visual cortex. CONCLUSIONS: Our study suggested that 2 weeks of iTBS intervention may be a novel, efficacious treatment for vsWM deficits in TRS, which can modulate the activity of local brain regions. iTBS can provide a solution for clinical treatment of TRS and may help patients approach normalcy.

Accelerated intermittent theta-burst stimulation broadly ameliorates symptoms and cognition in Alzheimer's disease: A randomized controlled trial.

BACKGROUND: Deficits in associative memory (AM) are the earliest and most prominent feature of Alzheimer's disease (AD) and demonstrate a clear cause of distress for patients and their families. OBJECTIVE: The present study aimed to determine AM enhancements following accelerated intermittent theta-burst stimulation (iTBS) in patients with AD. METHODS: In a randomized, double-blind, sham-controlled design, iTBS was administered to the left dorsolateral prefrontal cortex (DLPFC) of patients with AD for 14 days. Measurements included AM (primary outcome) and a comprehensive neuropsychological battery. Patients were evaluated at baseline, following the intervention (week 2), and 8 weeks after treatment cessation (week 10). RESULTS: Sixty patients with AD were initially enrolled; 47 completed the trial. The active group displayed greater AM improvements compared with the sham group at week 2 (P = 0.003), which was sustained at week 10. Furthermore, higher Mini-Mental State Examination (MMSE) scores at baseline were associated with greater AM improvements at weeks 2 and 10. For the independent iTBS group, this correlation predicted improvements in AM (P < 0.001) and identified treatment responders with 92% accuracy. Most of the neuropsychological tests were markedly improved in the active group. In particular, the Montreal Cognitive Assessment and MMSE in the active group increased by 2.8 and 2.3 points, respectively, at week 2, while there was no marked change in the sham group. CONCLUSION: In the present study, accelerated iTBS of the DLPFC demonstrated an effective and well-tolerated complementary treatment for patients with AD, especially for individuals with relatively high MMSE scores.

Intermittent Theta Burst Stimulation (iTBS) as an Optimal Treatment for Schizophrenia Risk Decision: an ERSP Study.

Objective: People with schizophrenia have serious impairments in social function, especially in decision-making ability. Transcranial magnetic stimulation modified intermittent theta burst transcranial magnetic stimulation (iTBS) has been shown to regulate the functional connection of brain networks. Our study explored the therapeutic effect of iTBS on decision-making disorders in schizophrenia. Methods: Participants were pseudorandomized and assigned to iTBS (n = 16) or sham (n = 16) group. iTBS group was administered 1,800 pulses on the target of the left dorsol lateral prefrontal cortex (L-DLPFC) per day for 14 consecutive days. We compared Iowa gambling task performance and associated event-related spectral perturbation results (ERSP) among two groups. Results: The results show that participants' performance in the high-lose in the iTBS group had stronger stimulation of theta spectral power than those in the sham group. Specifically, we found that under high-risk conditions, compared with the control group, the iTBS group showed significant activation of the theta spectrum power in the FPZ, FZ, FCZ, and CZ regions after treatment. Conclusions: Our results provide evidence that long-term iTBS stimulation effectively improves the decision-making ability of schizophrenia. After receiving negative feedback, patients can turn to safety options. These findings support that iTBS may be a potential treatment for clinical decision-making disorders.

Better modulation for risk decision-making after optimized magnetic stimulation.

Traditional repetitive transcranial magnetic stimulation can only produce a significant but weak effect on the cortex while theta burst stimulation (TBS), a patterned accelerated form of stimulation, can produce a stronger poststimulation effect, which may improve decision-making abilities. We designed a comparative assessment of the effect of intermittent TBS (iTBS), 20 Hz, in two risk decision-making tasks on healthy controls. Participants were randomized and assigned to the iTBS (n = 29), 20 Hz (n = 29), or sham (n = 29) groups. The effects of the different methods of left dorsolateral prefrontal cortex stimulation on risk decision-making functions were compared based on subjects' performance in the Game of Dice Task (GDT) and Risky Gains Task (RGT). The main indicators were positive and negative feedback utilization rates of GDT and RGT. Both iTBS and 20 Hz stimulation resulted in significant improvements upon negative feedback in the GDT, with increases in safe options and reductions in risky options; iTBS stimulation increased subjects' use of positive feedback in the GDT and RGT (all p < 0.05). Furthermore, the iTBS group had a stronger feedback risk reduction effect than the 20 Hz or sham group following RGT negative feedback (p < 0.05). Individuals would integrate positive and negative information more efficiently, leading to them making rational choices after excitatory transcranial magnetic stimulation. Moreover, iTBS has a stronger risk reduction effect following negative feedback than the 20Hz stimulation did. In summary, iTBS might have clinical value in decision promotion.

The Retinal Vessel Density Can Reflect Cognitive Function in Patients with Alzheimer's Disease: Evidence from Optical Coherence Tomography Angiography.

BACKGROUND: There is increasing evidence that Alzheimer's disease (AD) patients may present decreased cerebral blood perfusion before pathological brain changes. Using the retina as a window to the brain, we can study disorders of the central nervous system through the eyes. OBJECTIVE: This study aimed to investigate differences in retinal structure and vessel density (VD) between patients with mild AD and healthy controls (HCs). Furthermore, we explored the relationship between retinal VD and cognitive function. METHODS: We enrolled 37 patients with AD and 29 age-matched HCs who underwent standard ophthalmic optical coherence tomography angiography (OCTA) for evaluation of the retinal layer thickness and VD parameters. Cognitive function was evaluated using a battery of neuropsychological assessments. Finally, the correlations among retinal layer thickness, VD parameters, and cognitive function were evaluated. RESULTS: The retinal fiber layer thickness and retinal VD of patients with AD were significantly reduced compared with HCs. The retinal VD was significantly correlated with overall cognition, memory, executive, and visual-spatial perception functions. However, there was no significant between-group difference in the macular thickness. CONCLUSION: Our findings indicate a positive correlation between retinal VD and some, but not all, cognitive function domains. Most importantly, we demonstrated the role of OCTA in detecting early capillary changes, which could be a noninvasive biomarker for early AD.

Increased Accuracy of Emotion Recognition in Individuals with Autism-Like Traits after Five Days of Magnetic Stimulations.

Individuals with autism-like traits (ALT) belong to a subclinical group with similar social deficits as autism spectrum disorders (ASD). Their main social deficits include atypical eye contact and difficulty in understanding facial expressions, both of which are associated with an abnormality of the right posterior superior temporal sulcus (rpSTS). It is still undetermined whether it is possible to improve the social function of ALT individuals through noninvasive neural modulation. To this end, we randomly assigned ALT individuals into the real (n = 16) and sham (n = 16) stimulation groups. All subjects received five consecutive days of intermittent theta burst stimulation (iTBS) on the rpSTS. Eye tracking data and functional magnetic resonance imaging (fMRI) data were acquired on the first and sixth days. The real group showed significant improvement in emotion recognition accuracy after iTBS, but the change was not significantly larger than that in the sham group. Resting-state functional connectivity (rsFC) between the rpSTS and the left cerebellum significantly decreased in the real group than the sham group after iTBS. At baseline, rsFC in the left cerebellum was negatively correlated with emotion recognition accuracy. Our findings indicated that iTBS of the rpSTS could improve emotion perception of ALT individuals by modulating associated neural networks. This stimulation protocol could be a vital therapeutic strategy for the treatment of ASD.

Common variant of CNTNAP2 gene modulate the social performances and functional connectivity of posterior right temporoparietal junction.

Social deficits are features of autism and highly heritable traits. A common variant in autism-related CNTNAP2 gene, rs2710102, has been linked with social performance, but the neural substrates are largely unknown. We investigated variations in social performance and functional connectivity (static and dynamic) in the subregions of right temporoparietal junction (RTPJ), a key node of brain social network, using resting-state magnetic resonance imaging (n = 399) by genotype at rs2710102 in healthy volunteers. Social performance was evaluated using the social domain of the Autism-Spectrum Quotient (AQ-social; n = 641) and fixation time on eye areas during an eye-tracking task (n = 32). According to previous evidence that the A-allele is the risk allele for social dysfunction, we classified participants into GG and A-allele carriers (AA/AG) groups. The A-allele carriers showed poor social performance (high AQ-social and short fixation time on eye areas) compared with the GG carriers. In the A-allele carriers, decreased stationary functional connectivity between the orbitofrontal cortex and posterior RTPJ (pRTPJ), and decreased dynamic functional connectivity (dFC) between the medial prefrontal cortex (mPFC) and pRTPJ were observed. The fixation time at eye areas positively were correlated with the pRTPJ-mPFC dFC. These findings provided insight for genetic effect on social behavior and its potential neural substrate.

The Effect of High-Definition Transcranial Direct Current Stimulation of the Right Inferior Frontal Gyrus on Empathy in Healthy Individuals.

Empathy, including cognitive and emotional empathy, refers to the ability to infer the mental states of others and to the capacity to share emotions. The neural mechanisms involved in empathy are complex and not yet fully understood, and previous studies have shown that both cognitive and emotional empathy are closely associated with the inferior frontal gyrus (IFG). In this study, we examined whether empathy can be modulated by high-definition transcranial direct current stimulation (HD-tDCS) of the right IFG. Twenty-three healthy participants took part in all three experimental conditions (i.e., anodal, cathodal and sham stimulation) in a randomized order. Participants then completed the Chinese version of the Multifaceted Empathy Test (MET), which assesses both cognitive and emotional empathy. The results show that scores obtained for cognitive empathy following cathodal stimulation are significantly lower than those obtained following sham stimulation. In addition, scores obtained for cognitive empathy following anodal stimulation are higher than those obtained following sham stimulation, though the difference is only marginally significant. However, the results fail to show whether the stimulation of the right IFG via HD-tDCS plays a role in emotional empathy. Our results suggest that the right IFG plays a key role in cognitive empathy and indicate that HD-tDCS can regulate cognitive empathy by inducing excitability changes in the right IFG.

Slow Binocular Rivalry as a Potential Endophenotype of Schizophrenia.

Objectives: Binocular rivalry is a typical example of bistable perception that arises when two monocular images are simultaneously presented to each eye. Binocular rivalry is a heritable perceptual cognitive function that is impaired in patients with schizophrenia (SZ). Despite its potential suitability as a visual endophenotype, binocular rivalry has hardly been studied in the unaffected siblings of schizophrenia (SIB). There is also little research about whether binocular rivalry is a potential visual endophenotype between SZ and SIB. Methods: In our cross-sectional study, we included 40 SZ and their unaffected SIBs, as well as 40 age- and sex-matched healthy controls (HC). All subjects underwent the binocular rivalry test, the Positive and Negative Syndrome Scale (PANSS) and a battery of cognitive neuropsychological assessments evaluating attention, memory and executive function domains. Results: Our results demonstrate that the switching rate in SZ was significantly slower than in HC (p < 0.001), and compared to the SIB, the mean alternation rates were significantly different (p < 0.01). Moreover, there was a significant difference in mean switching rate between the SIB and the HC (p < 0.001). There was no significant correlation between the alternation rate of binocular rivalry and these cognitive tasks and the PANSS scores. Conclusion: The present study shows that SZ and SIB both exhibit changes in binocular rivalry, with SIB exhibiting intermediate performance compared with that of SZ and the HC. This supports the claim that the switching rate for SZ differs from that of SIB and suggests that binocular rivalry may qualify as a visual endophenotype for SZ.

Increased delayed reward during intertemporal decision-making in schizophrenic patients and their unaffected siblings.

Intertemporal choices are decisions with consequences in multiple time periods and constitute a significant part of social cognition. The shared neuropathological characteristics of patients with schizophrenia and their siblings might express intermediate phenotypes in behavior that could be used to further characterize the illness. Schizophrenic patients, unaffected siblings, and healthy controls underwent a computerized version of the "Intertemporal Choice Task". All participants could choose between sooner-smaller (SS) and later-larger (LL) options in now-trials and in not-now-trials. Subjects also underwent a battery of cognitive neuropsychological assessment. Our results indicated that schizophrenic patients and unaffected siblings both had a tendency to choose LL options in now-trials or not-now-trials compared to healthy controls. Schizophrenic patients had significantly lower scores in several cognitive tasks, including MoCA, attention, executive functions, and information processing when compared with the other two groups. Moreover, within the schizophrenic patient group, significant correlations were found between intertemporal decision-making performance and executive function. The present study showed that both schizophrenic patients and unaffected siblings preferred to choose larger-delayed rewards during intertemporal decision-making, which may result from frontal-striatal and frontal-parietal network dysfunction. Their intertemporal decision-making performance was associated with executive function performance.