Background
Over 55 million people worldwide are currently diagnosed with Alzheimer’s disease (AD) and live with debilitating episodic memory deficits (World Health Organization, 2022). Current ...pharmacological treatments have limited efficacy. Recently, transcranial alternating current stimulation (tACS) has shown memory improvement in AD by normalizing high‐frequency neuronal activity (Benussi et al., 2022). Our goal was to assess the safety, feasibility, and preliminary effects on episodic memory of a caregiver‐led home‐based tACS approach (HB‐tACS).
Method
8 participants diagnosed with AD (Table 1) underwent high‐definition HB‐tACS (40 Hz, 20‐minutes) targeting the left angular gyrus (AG), a key node of the memory network. The Acute Phase comprised 14‐weeks of HB‐tACS with at least five weekly sessions. Three participants underwent resting‐state electroencephalography (EEG) before and after. Subsequently, participants completed a 2–3‐month Hiatus Phase not receiving tACS. In the Taper Phase, participants received 2‐3 sessions per week over 3‐months. Primary outcomes were memory and global cognition, measured with the Memory Index Score (MIS) and Montreal Cognitive Assessment (MoCA), respectively, and EEG theta/gamma ratio. Results reported as mean±SD.
Result
All participants completed the study with, on average, 97 HB‐tACS sessions; reporting mild side effects during 25% of sessions, moderate during 5%, and severe during 1%. Acute Phase adherence was 98±6.8% and Taper Phase was 125±22.3% (from minimum of 2/week). After the Acute Phase, all participants showed memory improvement, MIS of 7.25±3.77, sustained during Hiatus 7.00±4.90 and Taper 4.63±2.39 Phases (Table 2), and decreased theta/gamma ratio in AG (Figure 1A). Conversely, participants did not show improvement in the MoCA, 1.13±3.80 after the Acute Phase, and there was modest decrease during the Hiatus ‐0.64± 3.28 and Taper ‐2.56±5.03 phases. These results suggest the specificity of the intervention for memory functioning (Figure 1B) and relate improvement to decreased theta/gamma ratio.
Conclusion
This pilot study shows the feasibility of a novel, remotely supervised, caregiver‐led HB‐tACS intervention for AD. Targeting the left AG, memory was noticeably improved while global cognition was relatively stable, indicating that future interventions might benefit from multifocal neuromodulation targeting multiple cognitive domains. These results are encouraging for the prospect of safe and feasible treatment within patients’ homes.
Background
Markers sensitive to brain changes at the transition from mild cognitive impairment (MCI) to dementia due to Alzheimer’s disease (AD) are needed for aiding prognosis and the selection of ...potential responders to novel interventional therapies. EEG markers may be advantageous due to their accessibility.
Prior research suggests that AD is associated with a shift in the brain’s oscillatory activity from higher to lower frequencies which can be captured as changes in the EEG spectral power ratio (SPR: α + β /δ + θ), a measurement associated with executive function1. The aim of the present study is to extend these findings to the prodromal stage of AD, and test the association of the SPR with amyloid burden.
Method
Data was obtained from 31 participants, including 23 aMCI (17 amyloid positive: Aβ+aMCI) and 14 CU individuals. We compared the SPRs between Aβ+aMCI and CU individuals, and tested its correlation with composite scores of executive functions, learning and memory, dementia severity, as well as amyloid load in the Aβ+aMCI group. Test‐retest reliability of the SPR was also inspected and the SPR of MCI individuals with different amyloid status was explored in hypothesis generating analyses.
Result
The SPR was significantly lower in the Aβ+aMCI group compared to the CU group (p = 0.0271) and was significantly correlated with Executive Function scores (r = 0.5634). The SPR showed excellent test‐retest reliability (rAβ+aMCI = 0.8629 and rCU = 0.9786). Logistic regression suggested that aMCI participants with a lower SPR had an increased probability of a positive amyloid PET.
Conclusion
Our results extended previous findings in AD and suggested that the SPR may be sensitive to pathophysiological changes in aMCI individuals in a cognitively meaningful manner. Further research may confirm these findings and may explore the potential of this measure to aid in the classification of aMCI individuals according to their amyloid status.
1. Benwell CSY, Davila‐Pérez P, Fried PJ, Jones RN, Travison TG, Santarnecchi E, Pascual‐Leone A, Shafi MM (2020) EEG spectral power abnormalities and their relationship with cognitive dysfunction in patients with Alzheimer’s disease and type 2 diabetes. Neurobiol Aging
85, 83‐95.
Abstract
Background
Distinguishing mild cognitive impairment (MCI) and Alzheimer’s disease‐related dementia (ADRD) requires assessing the clinical impact of cognitive deficits on a patient’s ...activities of daily living. To accurately monitor cognitive decline, it is thus critical to combine early screening of cognitive deficits with the assessment of functional impairment. The Digital Clock and Recall (DCR™), consisting of DCTclock™ and a 3‐word delayed recall, employs AI‐enabled performance analyses to evaluate memory, executive function, visuospatial abilities, and motor functions. The Life and Health Questionnaire (LHQ) is a brief digital survey that captures key lifestyle and health factors for cognitive decline/dementia. We evaluated whether the combination of the DCR and LHQ can predict functional status, measured by the Functional Abilities Questionnaire (FAQ) reported by an informant, in older individuals with statuses ranging from cognitively unimpaired to MCI and ADRD.
Method
849 participants from a multisite study (age mean±SD = 72.1±6.7; 56.8% female; years of education mean±SD = 15.4±2.7), classified as cognitively unimpaired (n = 369), MCI (n = 262), or ADRD (n = 215). Mild (mFD) and moderate (modFD) levels of functional dependence were defined as FAQ score ≥ 6 and ≥ 9, respectively. We conducted 10‐fold cross‐validated regularized logistic regressions using LHQ responses and DCR metrics to predict mFD or modFD, controlling for age, sex, and education.
Result
LHQ significantly predicted mFD and modFD (p’s<0.001, R2 = 0.13, and R2 = 0.12). Adding DCR metrics to the model improved both models (p’s<0.001, R2’s = 0.18 and 0.13, respectively). Surviving LHQ questions for predicting mFD related to unintended weight loss, social engagement/volunteering, cognitively stimulating tasks, sleep, and life satisfaction/purpose. Surviving LHQ questions for predicting modFD related to unintended weight loss, social engagement/volunteering, cognitively stimulating tasks, and sleep.
Conclusion
A brief assessment that can be completed in primary care settings in <10 min consisting of an objective digital cognitive assessment and a survey of self‐reported lifestyle and health factors can not only identify early cognitive impairment but also reliably predict level of functional dependence in instrumental activities of daily living ‐ without need for an informant.
Abstract
Background
Nearly 6.7 million people aged 65 and older in the US are living with Alzheimer’s disease (AD). Early detection of dementia presents a difficult challenge, as the earliest signs ...of cognitive decline often go undetected. Thus, more sensitive and clinically meaningful cognitive screening tools are needed. Evaluating the patient’s dependence in activities of daily living is critical to detect progression toward dementia. The Linus Health DCTclock™ employs AI‐enabled analyses of the clock drawing process to evaluate cognitive and motor function. We evaluated the utility of four DCTclock composite scales including Spatial Reasoning, Drawing Efficiency, Information Processing, and Motor Skills, 22 DCTclock subscales, and the 3‐word Delayed Recall score from the Digital Clock and Recall (DCR™) to predict the informant‐rated functional activities questionnaire (FAQ) score in older adults ranging from cognitively unimpaired to individuals with mild cognitive impairment (MCI) and AD‐related dementia (ADRD).
Method
939 participants in a multisite study (age mean±SD = 72.1±6.7; 57.1% female; years of education mean±SD = 15.4±2.7; primary language English), classified as cognitively unimpaired (n = 406), MCI (n = 293), or ADRD (n = 238) were included. We conducted cross‐validated regularized logistic regressions with FAQ score ≥6 or ≥9 (mild or moderate functional impairment, respectively) as dependent variable and DCTclock composite scales, subscales, and Delayed Recall score as predictors, in addition to age, sex, and education.
Result
Combination of DCTclock subscales and Delayed Recall predicted FAQ≥6 and ≥9 with AUCs = 0.79 and 0.81, respectively. DCTclock composite scales predicted FAQ≥ 6 and ≥9 with AUCs = 0.75 and 0.77, respectively. Combination of DCTclock composite scales and Delayed Recall predicted FAQ≥6 and ≥9 with AUCs = 0.77 and 0.79, respectively. DCTclock subscales by themselves predicted FAQ≥6 and ≥9 with AUCs = 0.77 and 0.79, respectively.
Conclusion
The DCR, a brief digital cognitive assessment with automatic scoring that can be completed in primary‐care settings, can infer the effect of cognitive impairment on a patient’s functional activity with great accuracy and within a few minutes. This makes the DCR an empowering tool for primary‐care providers in practical evaluation of patients with cognitive impairment.
Introduction A rapid and reliable neuropsychological protocol is essential for the efficient assessment of neurocognitive constructs related to emergent neurodegenerative diseases. We developed an ...AI-assisted, digitally administered/scored neuropsychological protocol that can be remotely administered in ~10 min. This protocol assesses the requisite neurocognitive constructs associated with emergent neurodegenerative illnesses. Methods The protocol was administered to 77 ambulatory care/memory clinic patients (56.40% women; 88.50% Caucasian). The protocol includes a 6-word version of the Philadelphia (repeatable) Verbal Learning Test P(r)VLT, three trials of 5 digits backward from the Backwards Digit Span Test (BDST), and the “animal” fluency test. The protocol provides a comprehensive set of traditional “core” measures that are typically obtained through paper-and-pencil tests (i.e., serial list learning, immediate and delayed free recall, recognition hits, percent correct serial order backward digit span, and “animal” fluency output). Additionally, the protocol includes variables that quantify errors and detail the processes used in administering the tests. It also features two separate, norm-referenced summary scores specifically designed to measure executive control and memory. Results Using four core measures, we used cluster analysis to classify participants into four groups: cognitively unimpaired (CU; n = 23), amnestic mild cognitive impairment (MCI; n = 17), dysexecutive MCI ( n = 23), and dementia ( n = 14). Subsequent analyses of error and process variables operationally defined key features of amnesia (i.e., rapid forgetting, extra-list intrusions, profligate responding to recognition foils); key features underlying reduced executive abilities (i.e., BDST items and dysexecutive errors); and the strength of the semantic association between successive responses on the “animal” fluency test. Executive and memory index scores effectively distinguished between all four groups. There was over 90% agreement between how cluster analysis of digitally obtained measures classified patients compared to classification using a traditional comprehensive neuropsychological protocol. The correlations between digitally obtained outcome variables and analogous paper/pencil measures were robust. Discussion The digitally administered protocol demonstrated a capacity to identify patterns of impaired performance and classification similar to those observed with standard paper/pencil neuropsychological tests. The inclusion of both core measures and detailed error/process variables suggests that this protocol can detect subtle, nuanced signs of early emergent neurodegenerative illness efficiently and comprehensively.
Neural correlates of Eureka moment Sprugnoli, Giulia; Rossi, Simone; Emmendorfer, Alexandra ...
Intelligence (Norwood),
20/May , Letnik:
62
Journal Article
Recenzirano
Odprti dostop
Insight processes that peak in “unpredictable moments of exceptional thinking” are often referred to as Aha! or Eureka moments. During insight, connections between previously unrelated concepts are ...made and new patterns arise at the perceptual level while new solutions to apparently insolvable problems suddenly emerge to consciousness. Given its unpredictable nature, the definition, and behavioral and neurophysiological measurement of insight problem solving represent a major challenge in contemporary cognitive neuroscience. Numerous attempts have been made, yet results show limited consistency across experimental approaches. Here we provide a comprehensive overview of available neuroscience of insight, including: i) a discussion about the theoretical definition of insight and an overview of the most widely accepted theoretical models, including those debating its relationship with creativity and intelligence; ii) an overview of available tasks used to investigate insight; iii) an ad-hoc quantitative meta-analysis of functional magnetic resonance imaging studies investigating the Eureka moment, using activation likelihood estimation maps; iv) a review of electroencephalographic evidence in the time and frequency domains, as well as v) an overview of the application of non-invasive brain stimulation techniques to causally assess the neurobiological basis of insight as well as enhance insight-related cognition.
•EEG data suggest a primary role for alpha oscillations in prefrontal and parietal lobes.•fMRI data do not support overall right hemispheric dominance during Eureka moments.•Right temporal lobe shows concordant activations across fMRI and EEG studies.•Need for a consensus around validated insight tasks to be used for EEG/fMRI studies.•Future studies should test for causal role of brain areas by modulating brain oscillations.
Because neuroimaging studies have shown that cue-provoked smoking craving is associated with changes in the activity of the bilateral dorsolateral prefrontal cortex (DLPFC), we aimed to investigate ...whether a powerful technique of noninvasive brain stimulation, transcranial direct current stimulation (tDCS), reduces cue-provoked smoking craving as indexed by a visual analog scale.
We performed a randomized, sham-controlled crossover study in which 24 subjects received sham and active tDCS (anodal tDCS of the left and right DLPFC) in a randomized order. Craving was induced by cigarette manipulation and exposure to a smoking video. The study ran from January 2006 to October 2006.
Smoking craving was significantly increased after exposure to smoking-craving cues (p < .0001). Stimulation of both left and right DLPFC with active, but not sham, tDCS reduced craving significantly when comparing craving at baseline and after stimulation, without (p = .007) and with (p = .005) smoking-craving cues. There were no significant mood changes in any of the conditions of stimulation. Adverse events were mild and distributed equally across all treatment conditions.
Our findings extend the results of a previous study on the use of brain stimulation to reduce craving, showing that cortical stimulation with tDCS is beneficial for reducing cue-provoked craving, and thus support the further exploration of this technique for smoking cessation.
Objective. To determine the effects of a transcranial direct current
stimulation (tDCS) intervention with the anode placed over the left dorsolateral
prefrontal cortex (dlPFC) and cathode over the ...right supraorbital region, on cognition,
mobility, and “dual-task” standing and walking in older adults with mild-to-moderate motor
and cognitive impairments. Methods. A double-blinded, block-randomized,
sham-controlled trial was conducted in 18 nondemented, ambulatory adults aged ⩾65 years
with slow walking speed (⩽1.0 m/s) and “executive” dysfunction (Trail Making Test B score
⩽25th percentile of age- and education-matched norms). Interventions included ten
20-minute sessions of tDCS or sham stimulation. Cognition, mobility, and dual-task
standing and walking were assessed at baseline, postintervention, and 2 weeks thereafter.
Dual tasking was also assessed immediately before and after the first tDCS session.
Results. Intervention compliance was high (mean ± SD = 9.5 ± 1.1
sessions) and no unexpected or serious side effects were reported. tDCS, compared with
sham, induced improvements in the Montreal Cognitive Assessment total score
(P = .03) and specifically within the executive function subscore of
this test (P = .002), and in several metrics of dual-task standing and
walking (P < .05). Each of these effects persisted for 2 weeks. tDCS
had no effect on the Timed Up-and-Go test of mobility or the Geriatric Depression Scale.
Those participants who exhibited larger improvements in dual-task standing posture
following the first tDCS session exhibited larger cognitive-motor improvements following 2
weeks of tDCS (P < .04). Interpretation. tDCS
intervention designed to stimulate the left dorsolateral prefrontal cortex may improve
executive function and dual tasking in older adults with functional limitations.
Integrating TMS with EEG: How and What For Thut, Gregor; Pascual-Leone, Alvaro
Brain topography,
2010, 1-2010, 2010-Jan, 2010-1-00, 20100101, Letnik:
22, Številka:
4
Journal Article
Recenzirano
Issue Title: Special Topic: Integrating TMS with EEG: How and what for?; Guest Editors: Gregor Thut and Alvaro Pascual-Leone.
•We tested if mechanisms of plasticity predicted rTMS clinical outcome.•We compared 10 Hz rTMS and iTBS plasticity measures.•10Hz-induced modulation predicted 10 Hz treatment outcome.•iTBS-induced ...modulation did not broadly correlate with 10 Hz treatment response.
Many patients with treatment-resistant depression (TRD) respond to repetitive transcranial magnetic stimulation (rTMS) treatment. This study aimed to investigate whether modulation of corticomotor excitability by rTMS predicts response to rTMS treatment for TRD in 10 Hz and intermittent theta-burst stimulation (iTBS) protocols.
Thirteen TRD patients underwent two evaluations of corticomotor plasticity—assessed as the post-rTMS (10 Hz, iTBS) percent change (%∆) in motor evoked potential (MEP) amplitude elicited by single-pulse TMS. Following corticomotor plasticity evaluations, patients subsequently underwent a standard 6-week course of 10 Hz rTMS (4 s train, 26 s inter-train interval, 3000 total pulses, 120% of motor threshold) to the left dorsolateral prefrontal cortex. Treatment efficacy was assessed by the Beck Depression Inventory II (BDI-II) and Hamilton Depression Rating Scale (HAM-D). The change in MEPs was compared between 10 Hz and iTBS conditions and related to the change in BDI-II and HAM-D scores.
Analyses of variance revealed that across all time-points, higher post-10 Hz MEP change was a significant predictor of greater improvement on the BDI-II (p < 0.001) and HAM-D (p = 0.022). This relationship was not observed with iTBS (p-values≥0.100). Post-hoc tests revealed the MEP change 20 min post-10 Hz was the strongest predictor of BDI-II improvement.
Cortical excitability was measured from the motor cortex, rather than the dorsolateral prefrontal cortex, where treatment is applied. The 10 Hz and iTBS protocols were performed at different intensities consistent with common practice.
Modulation of corticomotor excitability by 10 Hz can predict response to rTMS treatment with 10 Hz rTMS.
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