Differential Effects of Continuous Theta Burst Stimulation over the Bilateral and Unilateral Cerebellum on Working Memory.

Recent functional MRI studies have implicated the cerebellum in working memory (WM) alongside the prefrontal cortex. Some findings indicate that the right cerebellum is activated during verbal tasks, while the left is engaged during visuospatial tasks, suggesting cerebellar lateralization in WM function. The cerebellum could be a potential target for non-invasive brain stimulation (NIBS) to enhance WM function in cognitive disorders. However, the comprehensive influence of cerebellar lateralization on different types of WM and the effect of stimulation over the unilateral or bilateral cerebellum remain uncertain. This study was to investigate the cerebellum's functional lateralization and its specific impact on various aspects of WM in a causal manner using unilateral or bilateral cerebellar continuous theta burst stimulation (cTBS), a form of inhibitroy NIBS. Twenty-four healthy participants underwent four sessions of cTBS targeting the left, right, or bilateral Crus I of the cerebellum, or a sham condition, in a controlled cross-over design. WM performance was assessed pre- and post-stimulation using neuropsychological tests, including the 3-back task, spatial WM task, and digit span task. Results indicated that cTBS over the bilateral and right cerebellum both led to a greater improvement in 3-back task performance compared to sham stimulation. Additionally, active cTBS over the bilateral cerebellum yielded better performance in the spatial WM task than sham stimulation. However, no significant differences were observed between stimulation conditions for the auditory digit span task. This study may provide novel causal evidence highlighting the specific involvement of the right and bilateral cerebellum in various types of WM. Specifically, the right cerebellum appears crucial for updating and tracking 3-back WM content, while spatial WM processes require the coordinated engagement of both cerebellar hemispheres.

Glaucoma Rehabilitation using ElectricAI Transcranial Stimulation (GREAT)-study protocol for randomized controlled trial using combined perceptual learning and transcranial electrical stimulation for vision enhancement.

BACKGROUND: Glaucoma patients with irreversible visual field loss often experience decreased quality of life, impaired mobility, and mental health challenges. Perceptual learning (PL) and transcranial electrical stimulation (tES) have emerged as promising interventions for vision rehabilitation, showing potential in restoring residual visual functions. The Glaucoma Rehabilitation using ElectricAI Transcranial stimulation (GREAT) project aims to investigate whether combining PL and tES is more effective than using either method alone in maximizing the visual function of glaucoma patients. Additionally, the study will assess the impact of these interventions on brain neural activity, blood biomarkers, mobility, mental health, quality of life, and fear of falling. METHODS: The study employs a three-arm, double-blind, randomized, superiority-controlled design. Participants are randomly allocated in a 1:1:1 ratio to one of three groups receiving: (1) real PL and real tES, (2) real PL and sham tES, and (3) placebo PL and sham tES. Each participant undergoes 10 sessions per block (~ 1 h each), with a total of three blocks. Assessments are conducted at six time points: baseline, interim 1, interim 2, post-intervention, 1-month post-intervention, and 2-month post-intervention. The primary outcome is the mean deviation of the 24-2 visual field measured by the Humphrey visual field analyzer. Secondary outcomes include detection rate in the suprathreshold visual field, balance and gait functions, and electrophysiological and biological responses. This study also investigates changes in neurotransmitter metabolism, biomarkers, self-perceived quality of life, and psychological status before and after the intervention. DISCUSSION: The GREAT project is the first study to assess the effectiveness of PL and tES in the rehabilitation of glaucoma. Our findings will offer comprehensive assessments of the impact of these treatments on a wide range of brain and vision-related metrics including visual field, neural activity, biomarkers, mobility, mental health, fear of falling, and quality of life. TRIAL REGISTRATION: ClinicalTrials.gov NCT05874258 . Registered on May 15, 2023.

Neural correlates of impaired learning and recognition of novel faces in mild cognitive impairment.

OBJECTIVE: Face memory impairment significantly affects social interactions and daily functioning in individuals with mild cognitive impairment (MCI). While deficits in recognizing familiar faces among individuals with MCI have been reported, their ability to learn and recognize unfamiliar faces remains unclear. This study examined the behavioral performance and event-related potentials (ERPs) of unfamiliar face memorization and recognition in MCI. METHODS: Fifteen individuals with MCI and 15 healthy controls learned and recognized 90 unfamiliar neutral faces. Their performance accuracy and cortical ERPs were compared between the two groups across the learning and recognition phases. RESULTS: Individuals with MCI had lower accuracy in identifying newly learned faces than healthy controls. Moreover, individuals with MCI had reduced occipitotemporal N170 and central vertex positive potential responses during both the learning and recognition phases, suggesting impaired initial face processing and attentional resources allocation. Also, individuals with MCI had reduced central N200 and frontal P300 responses during the recognition phase, suggesting impaired later-stage face recognition and attention engagement. CONCLUSION: These findings provide neurobehavioral evidence for impaired learning and recognition of unfamiliar faces in individuals with MCI. SIGNIFICANCE: Individuals with MCI may have face memory deficits in both early-stage face processing and later-stage recognition .

Right, but not left, posterior superior temporal gyrus is causally involved in vocal feedback control.

The posterior superior temporal gyrus (pSTG) has been implicated in the integration of auditory feedback and motor system for controlling vocal production. However, the question as to whether and how the pSTG is causally involved in vocal feedback control is currently unclear. To this end, the present study selectively stimulated the left or right pSTG with continuous theta burst stimulation (c-TBS) in healthy participants, then used event-related potentials to investigate neurobehavioral changes in response to altered auditory feedback during vocal pitch regulation. The results showed that, compared to control (vertex) stimulation, c-TBS over the right pSTG led to smaller vocal compensations for pitch perturbations accompanied by smaller cortical N1 and larger P2 responses. Enhanced P2 responses received contributions from the right-lateralized temporal and parietal regions as well as the insula, and were significantly correlated with suppressed vocal compensations. Surprisingly, these effects were not found when comparing c-TBS over the left pSTG with control stimulation. Our findings provide evidence, for the first time, that supports a causal relationship between right, but not left, pSTG and auditory-motor integration for vocal pitch regulation. This lends support to a right-lateralized contribution of the pSTG in not only the bottom-up detection of vocal feedback errors but also the involvement of driving motor commands for error correction in a top-down manner.

Is a new feature learned behind a newly efficient color-orientation conjunction search?

It is well known that feature search is efficient, whereas conjunction search is usually inefficient. However, prior studies have shown that some conjunction search could become very efficient through perceptual learning, behaving like a traditional feature search. An unanswered question is whether a new feature is learned when an inefficient conjunction search become efficient after extensive training. A popular view is that the trained conjunction has been successfully unitized into a new feature and thus could pop out from neighboring distractors. Here, by using stimulus specificity and transfer of perceptual learning as an approach, we investigate whether a new feature is learned when an initially inefficient conjunction search becomes highly efficient after extensive training. In two experiments, we consistently found that long-term perceptual learning over days could induce an inefficient-to-efficient pattern change in a color-orientation conjunction search. Moreover, the learning effect of the conjunction target could partly transfer to a new target that shared a same color or a same orientation with the trained target. Remarkably, the total amount of the learning effect was approximately equal to the sum of the transfer effects of individual features. Such additive learning pattern could last for at least several months, although the learning of separate features showed different patterns of persistence. These results do not support that the trained conjunction is unitized into a new and inseparable feature after learning. Instead, our findings point to a feature-based attention enhancement mechanism underlying long-term perceptual learning and its persistence of color-orientation conjunction search.

The left inferior frontal gyrus is causally linked to vocal feedback control: evidence from high-definition transcranial alternating current stimulation.

Current models of speech motor control propose a role for the left inferior frontal gyrus (IFG) in feedforward control of speech production. There is evidence, however, that has implicated the functional relevance of the left IFG for the neuromotor processing of vocal feedback errors. The present event-related potential (ERP) study examined whether the left IFG is causally linked to auditory feedback control of vocal production with high-definition transcranial alternating current stimulation (HD-tACS). After receiving active or sham HD-tACS over the left IFG at 6 or 70 Hz, 20 healthy adults vocalized the vowel sounds while hearing their voice unexpectedly pitch-shifted by ±200 cents. The results showed that 6 or 70 Hz HD-tACS over the left IFG led to larger magnitudes and longer latencies of vocal compensations for pitch perturbations paralleled by larger ERP P2 responses than sham HD-tACS. Moreover, there was a lack of frequency specificity that showed no significant differences between 6 and 70 Hz HD-tACS. These findings provide first causal evidence linking the left IFG to vocal pitch regulation, suggesting that the left IFG is an important part of the feedback control network that mediates vocal compensations for auditory feedback errors.

A causal link between left supplementary motor area and auditory-motor control of vocal production: Evidence by continuous theta burst stimulation.

The supplementary motor area (SMA) has been implicated in the feedforward control of speech production. Whether this region is involved in speech motor control through auditory feedback, however, remains uncertain. The present event-related potential (ERP) study examined the role of the left SMA in vocal pitch regulation in a causal manner by combining auditory feedback manipulations and neuronavigated continuous theta bust stimulation (c-TBS). After receiving c-TBS over the left SMA or the control site (vertex), twenty young adults vocalized the vowel sound /u/ while hearing their voice unexpectedly pitch-shifted -50 or -200 cents. Compared to the control stimulation, c-TBS over the left SMA led to decreased vocal compensations for pitch perturbations of -50 and -200 cents. A significant decrease of N1 and P2 responses to -200 cents perturbations was also found when comparing active and control stimulation. Major neural generators of decreased P2 responses included the right-lateralized superior and middle temporal gyrus and angular gyrus. Notably, a significant correlation was found between active-control differences in the vocal compensation and P2 responses for the -200 cents perturbations. These findings provide neurobehavioral evidence for a causal link between the left SMA and auditory-motor integration for vocal pitch regulation, suggesting that the left SMA receives auditory feedback information and mediates vocal compensations for feedback errors in a bottom-up manner.

Continuous theta burst stimulation over left supplementary motor area facilitates auditory-vocal integration in individuals with Parkinson's disease.

Accumulating evidence suggests that impairment in auditory-vocal integration characterized by abnormally enhanced vocal compensations for auditory feedback perturbations contributes to hypokinetic dysarthria in Parkinson's disease (PD). However, treatment of this abnormality remains a challenge. The present study examined whether abnormalities in auditory-motor integration for vocal pitch regulation in PD can be modulated by neuronavigated continuous theta burst stimulation (c-TBS) over the left supplementary motor area (SMA). After receiving active or sham c-TBS over left SMA, 16 individuals with PD vocalized vowel sounds while hearing their own voice unexpectedly pitch-shifted two semitones upward or downward. A group of pairwise-matched healthy participants was recruited as controls. Their vocal responses and event-related potentials (ERPs) were measured and compared across the conditions. The results showed that applying c-TBS over left SMA led to smaller vocal responses paralleled by smaller P1 and P2 responses and larger N1 responses in individuals with PD. Major neural generators of reduced P2 responses were located in the right inferior and medial frontal gyrus, pre- and post-central gyrus, and insula. Moreover, suppressed vocal compensations were predicted by reduced P2 amplitudes and enhanced N1 amplitudes. Notably, abnormally enhanced vocal and P2 responses in individuals with PD were normalized by c-TBS over left SMA when compared to healthy controls. Our results provide the first causal evidence that abnormalities in auditory-motor control of vocal pitch production in PD can be modulated by c-TBS over left SMA, suggesting that it may be a promising non-invasive treatment for speech motor disorders in PD.

Does m-health-based exercise (guidance plus education) improve efficacy in patients with chronic low-back pain? A preliminary report on the intervention's significance.

BACKGROUND: The utilization of mobile health (m-health) has rapidly expanded during the COVID-19 pandemic, and there is still a lack of relevant clinical data pertaining to chronic low-back pain (CLBP) management. This study was designed to compare the effectiveness of m-health-based exercise (via guidance plus education) versus exercise (via guidance) during CLBP management. METHODS: Participants (n = 40) were randomly assigned to intervention and control groups. The intervention group received m-health-based exercise (via guidance plus education), whereas the control group received m-health-based exercise (via guidance). The exercise prescription video and educational content were sent to participants by the application (app), Ding Talk. Repeated-measures analysis of variance was used to test the baseline's intervention effects, 6-week follow-up, and 18-week follow-up. We selected function (Roland and Morris Disability Questionnaire) and pain intensity (current, mean, and most severe Numeric Rating Scale in the last 2 weeks) as the primary outcomes, changes of negative emotion (depression, anxious), and quality of life as the secondary outcomes. RESULTS: Time's significant effect was found in pain, function, and health-related quality of life in both groups, but time did not show significant interaction effects. Participants were able to use m-based education with their anxiety and depression after treatment, but the relief only lasted until week 6. No differences were found on the aspect of mental health-related quality of life. CONCLUSION: Preliminary findings suggest that m-health-based exercise (via guidance) may be a convenient and effective method to treat CLBP. However, additional health education didn't help more. More rigorous controlled trials are needed to improve the therapeutic effect in future studies. TRIAL REGISTRATION: Chinese Clinical Trials Registry Number ChiCTR2000041459 . Registered on December 26, 2020.

Continuous theta burst stimulation over left and right supramarginal gyri demonstrates their involvement in auditory feedback control of vocal production.

The supramarginal gyrus (SMG) has been implicated in auditory-motor integration for vocal production. However, whether the SMG is bilaterally or unilaterally involved in auditory feedback control of vocal production in a causal manner remains unclear. The present event-related potential (ERP) study investigated the causal roles of the left and right SMG to auditory-vocal integration using neuronavigated continuous theta burst stimulation (c-TBS). Twenty-four young adults produced sustained vowel phonations and heard their voice unexpectedly pitch-shifted by ±200 cents after receiving active or sham c-TBS over the left or right SMG. As compared to sham stimulation, c-TBS over the left or right SMG led to significantly smaller vocal compensations for pitch perturbations that were accompanied by smaller cortical P2 responses. Moreover, no significant differences were found in the vocal and ERP responses when comparing active c-TBS over the left vs. right SMG. These findings provide neurobehavioral evidence for a causal influence of both the left and right SMG on auditory feedback control of vocal production. Decreased vocal compensations paralleled by reduced P2 responses following c-TBS over the bilateral SMG support their roles for auditory-motor transformation in a bottom-up manner: receiving auditory feedback information and mediating vocal compensations for feedback errors.

Theta burst stimulation over left cerebellum does not modulate auditory feedback control of vocal production.

Background: Accumulating evidence has shown significant contributions of the right cerebellum to auditory-motor integration for vocal production. Whether the left cerebellum is likewise involved in vocal motor control, however, remains unclear. Methods: By applying neuronavigated continuous and intermittent theta burst stimulation (cTBS/iTBS) over the left cerebellar lobule VII (Crus I), the present event-related potential (ERP) study investigated whether the left cerebellum exerts causal effects in modulating auditory feedback control of vocal pitch production. After receiving cTBS, iTBS, or sham stimulation over the left cerebellum, a group of fifteen young adults produced sustained vowels while hearing their voice unexpectedly shifted in pitch upwards or downwards by 200 cents. The effects of cerebellar stimulation were assessed by measuring the vocal and ERP (N1/P2) responses to pitch perturbations across the conditions. Results: When compared to sham stimulation, cTBS or iTBS over the left cerebellar lobule VII (Crus I) led to no systematic changes in vocal compensations for pitch perturbations in auditory feedback. Also, the cortical N1/P2 responses did not vary significantly across the three stimulation sessions. Conclusion: These findings present the first neurobehavioral evidence suggesting that the left cerebellum is not causally associated with auditory feedback control of vocal production. Together with previously reported causal effects of the right cerebellum in modulating vocal pitch regulation, the present study lends support to the hypothesis that there is a functional lateralization of the cerebellum in vocal motor control though auditory feedback.

Onset Time of Inhibition of Return Is a Promising Index for Assessing Cognitive Functions in Older Adults.

OBJECTIVES: Developing efficient tools for assessing general cognitive functions in older adults is essential. Previous studies found that inhibition of return (IOR) occurred later in the older adults than in the younger. However, little is known about the relationship between the onset time of IOR (IOR-OT) and cognitive functions in the aging population. The present study examined this issue and investigated the potential of using IOR-OT as an index of cognitive functioning in older adults. METHODS: In two studies, the IOR-OT of healthy younger and older adults was measured by a modified Posner peripheral cueing task, and cognitive functions of the older adults were evaluated with the Addenbrooke's Cognitive Examination Revised (ACE-R). RESULTS: Both studies showed a significant correlation (r = ~.5) between IOR-OT and cognitive functions as assessed by ACE-R in older individuals: later IOR-OT was accompanied by a lower ACE-R score. DISCUSSION: To our knowledge, the present studies are the first to discover a relatively strong correlation between IOR-OT and cognitive functions in older adults. These findings provide new evidence supporting the inhibition deficit theory of aging and lay the foundation of using IOR-OT as an objective measure of cognitive functions in the aging population.

Working Memory Load Enhances the Attentional Capture of Low Reward History.

Attention priority of reward history, also called value-driven attentional capture (VDAC), is different from that of saliency or contingency. The magnitude of VDAC was found to be correlated with working memory capacity, but how cognitive control interacts with the attentional allocation of reward association is not clear. Here, we examined whether the distraction by learned color-reward association would change under different working memory load conditions. Participants were first trained with color-reward associations by searching a green/red circle with low/high reward. Then, during the test session, participants needed to search a unique shape while a green/red shape was either presented as a distractor or not shown at all. To manipulate the working memory load in the test, a digital memory task was integrated with the visual search task in half of the trials (memory load condition), but not in the other half (no-load condition). Consistent results were found in two experiments that the magnitude of attentional capture caused by low-value distractors was larger under memory load condition than under no-load condition, while there was no enough evidence supporting the influence of memory load on attentional capture by high-value distractors. These results suggested that working memory load, which occupied part of cognitive resources, reduced the priority of target information and might also modulate the strength of reward association holding in working memory. These findings extend the knowledge regarding the influence of working memory load on attentional capture of reward and suggest that reward-induced distraction is dynamic and could be modulated by cognitive control.

Unconscious versus conscious thought in creative science problem finding: Unconscious thought showed no advantage!

Unconscious thought theory (UTT) suggests that creativity benefits more from unconscious thought than conscious thought. However, previous studies have only focused on creative problem solving. This study aims to explore the effect of unconscious thought and conscious thought in creative science problem finding (CSPF). The ability of CSPF was measured by fluency, flexibility and originality. Participants accomplished the CSPF task after 3 min of distraction, during which unconscious thought was supposed to take place, or after 3 min of conscious thought. Results showed that unconscious thought had no advantage over conscious thought on CSPF. For the CSPF task with open instructions, conscious thought was comparable to unconscious thought in fluency, flexibility and originality. What's more, for the CSPF task with closed instructions, unconscious thought was even overtaken by conscious thought in fluency, flexibility and originality. These findings extend the unconscious thought theory and provide practical guidance on how to propose a creative science problem.