Improving Neurological Health in Aging Via Neuroplasticity-Based Computerized Exercise: Protocol for a Randomized Controlled Trial.

BACKGROUND: Our current understanding of how computerized brain training drives cognitive and functional benefits remains incomplete. This paper describes the protocol for Improving Neurological Health in Aging via Neuroplasticity-based Computerized Exercise (INHANCE), a randomized controlled trial in healthy older adults designed to evaluate whether brain training improves cholinergic signaling. OBJECTIVE: INHANCE evaluates whether 2 computerized training programs alter acetylcholine binding using the vesicular acetylcholine transporter ligand [18F] fluoroethoxybenzovesamicol ([18F] FEOBV) and positron emission tomography (PET). METHODS: In this phase IIb, prospective, double-blind, parallel-arm, active-controlled randomized trial, a minimum of 92 community-dwelling healthy adults aged 65 years and older are randomly assigned to a brain training program designed using the principles of neuroplasticity (BrainHQ by Posit Science) or to an active control program of computer games designed for entertainment (eg, Solitaire). Both programs consist of 30-minute sessions, 7 times per week for 10 weeks (35 total hours), completed remotely at home using either loaned or personal devices. The primary outcome is the change in FEOBV binding in the anterior cingulate cortex, assessed at baseline and posttest. Exploratory cognitive and behavioral outcomes sensitive to acetylcholine are evaluated before, immediately after, and 3 months following the intervention to assess the maintenance of observed effects. RESULTS: The trial was funded in September 2019. The study received approval from the Western Institutional Review Board in October 2020 with Research Ethics Board of McGill University Health Centre and Health Canada approvals in June 2021. The trial is currently ongoing. The first participant was enrolled in July 2021, enrollment closed when 93 participants were randomized in December 2023, and the trial will conclude in June 2024. The study team will be unblinded to conduct analyses after the final participant exits the study. We expect to publish the results in the fourth quarter of 2024. CONCLUSIONS: There remains a critical need to identify effective and scalable nonpharmaceutical interventions to enhance cognition in older adults. This trial contributes to our understanding of brain training by providing a potential neurochemical explanation of cognitive benefit. TRIAL REGISTRATION: ClinicalTrials.gov NCT04149457; https://clinicaltrials.gov/ct2/show/NCT04149457. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/59705.

Evaluating EEG neurofeedback in sport psychology: a systematic review of RCT studies for insights into mechanisms and performance improvement.

Electroencephalographic Neurofeedback Training (EEG NFT) aims to improve sport performance by teaching athletes to control their mental states, leading to better cognitive, emotional, and physical outcomes. The psychomotor efficiency hypothesis suggests that optimizing brain function could enhance athletic ability, indicating the potential of EEG NFT. However, evidence for EEG-NFT's ability to alter critical brain activity patterns, such as sensorimotor rhythm and frontal midline theta-key for concentration and relaxation-is not fully established. Current research lacks standardized methods and comprehensive studies. This shortfall is due to inconsistent EEG target selection and insufficient focus on coherence in training. This review aims to provide empirical support for EEG target selection, conduct detailed control analyses, and examine the specificity of electrodes and frequencies to relation to the psychomotor efficiency hypothesis. Following the PRISMA method, 2,869 empirical studies were identified from PubMed, Science Direct, Web of Science, Embase, CNKI, and PsycINFO. Thirteen studies met the inclusion criteria: (i) proficient skill levels; (ii) use of EEG; (iii) neurofeedback training (NFT); (iv) motor performance metrics (reaction time, precision, dexterity, balance); (v) control group for NFT comparison; (vi) peer-reviewed English-language publication; and (vii) randomized controlled trial (RCT) design. Studies indicate that NFT can enhance sports performance, including improvements in shooting accuracy, golf putting, and overall motor skills, as supported by the psychomotor efficiency hypothesis. EEG NFT demonstrates potential in enhancing sports performance by optimizing performers' mental states and psychomotor efficiency. However, the current body of research is hampered by inconsistent methodologies and a lack of standardized EEG target selection. To strengthen the empirical evidence supporting EEG NFT, future studies need to focus on standardizing target selection, employing rigorous control analyses, and investigating underexplored EEG markers. These steps are vital to bolster the evidence for EEG NFT and enhance its effectiveness in boosting sport performance.

Is working memory domain-general or domain-specific?

Given the fundamental role of working memory (WM) in all domains of cognition, a central question has been whether WM is domain-general. However, the term 'domain-general' has been used in different, and sometimes misleading, ways. By reviewing recent evidence and biologically plausible models of WM, we show that the level of domain-generality varies substantially between three facets of WM: in terms of computations, WM is largely domain-general. In terms of neural correlates, it contains both domain-general and domain-specific elements. Finally, in terms of application, it is mostly domain-specific. This variance encourages a shift of focus towards uncovering domain-general computational principles and away from domain-general approaches to the analysis of individual differences and WM training, favoring newer perspectives, such as training-as-skill-learning.

The effect of brain training video games on improving visuospatial working memory and executive function in children with dyscalculia.

The aim was to investigate the effect of brain training video games on improving visuospatial working memory and executive function in children with dyscalculia. This study employed a quasi-experimental, within-subjects design. Pre- post- and follow up test scores on visuospatial working memory and executive function were used. Sixty children from a primary education public school in Taif were selected. This study employed simple random method for selecting participants. Children assigned to the experimental group completed 18, 30 ms training sessions at the technology room in the presence of the researcher over a period of six weeks. The analyses were conducted using SPSS by performing a repeated-measures analysis of variance with a between-group factor and a with-group factor (pretest and posttest). Scheffé's post hoc test was also applied. The training helped the intervention group gain better scores in visuospatial working memory and executive function in post test compared to control one. There were significant differences in visuospatial working memory and executive function across different measurements(pre-post-and follow up).

Corrigendum: A conceptual view of cognitive intervention in older adults with and without cognitive decline-a systemic review.

[This corrects the article DOI: 10.3389/fragi.2022.844725.].

Efficacy and Concurrent Validity of Computerized Brain Training Based on Everyday Living (BTEL) Based on Instrumental Activities of Living for Cognitively Healthy Old Individuals: A Preliminary Study.

Background: Interventions to prevent or attenuate cognitive decline and dementia in older adults are becoming increasingly important. Recently, cognitive training exercise can be via computer or mobile technology for independent or home use. Recent meta-analysis has reported that Computerized Cognitive Training (CCT) is effective at enhancing cognitive function in healthy older and Alzheimer's disease adults, although little is known about individual characteristics of each computerized program. Objective: We developed a new CCT named Brain Training Based on Everyday Living (BTEL) to enhance cognitive capacity for Instrumental Activities of Daily Living (IADL). We aim to evaluate the efficacy of the BTEL among cognitively healthy old individuals and to explore its concurrent validity and construct concept. Methods: We conducted a double-blind study where 106 individuals aged 65 years and older (intervened = 53, control = 53) worked on the active and placebo tasks three times a week over three months (clinical trial: UMIN000048730). The main results were examined using ANCOVA and calculating correlation coefficients. Results: We found no effect on total score of the three tests; however, there was significant effect for the BTEL on: recognition in MMSE, and immediate recall in HDSR. The tasks are associated with prefrontal cortex. In addition, correlations indicated that each BTEL domain had some validity as a cognitive assessment tool. Different from previous CCT, we determined the neuropsychological characteristics of specific cognitive tasks of the BTEL to a certain degree. Conclusions: We found modest efficacy of the BTEL in cognitively healthy old individuals and confirmed its concurrent validity and the conceptual construct.

Terms of Engagement: Understanding the Motivations, Preferences, and Attitudes of Older Adults Toward Mobile Cognitive Assessment and Training.

BACKGROUND AND OBJECTIVES: The future of cognitive assessment is likely to involve mobile applications for smartphones and tablets; cognitive training is also often delivered in these formats. Unfortunately, low adherence to these programs can hinder efforts at the early detection of cognitive decline and interfere with examining cognitive training efficacy in clinical trials. We explored factors that increase adherence to these programs among older adults. RESEARCH DESIGN AND METHODS: Focus groups were conducted with older adults (N = 21) and a younger adult comparison group (N = 21). Data were processed using reflexive thematic analysis with an inductive, bottom-up approach. RESULTS: Three primary themes related to adherence were developed from the focus group data. Switches of engagement reflects factors that must be present; without them, engagement is unlikely. Dials of engagement reflects a cost-benefit analysis that users undergo, the outcome of which determines whether a person will be more or less likely to engage. Bracers of engagement reflects factors that nudge users toward engagement by minimizing barriers associated with the other themes. Older adults in general were more sensitive to opportunity costs, preferred more cooperative interactions, and were more likely to mention technology barriers. DISCUSSION AND IMPLICATIONS: Our results are important for informing the design of mobile cognitive assessment and training apps for older adults. These themes provide guidance about ways apps could be modified to increase engagement and adherence, which in turn can more effectively facilitate the early detection of cognitive impairment and the evaluation of cognitive training efficacy.

Train-your-brain program to reduce depression, anxiety, and stress in stroke survivors: a pilot community-based cognitive intervention study.

Introduction: Stroke is a major cause of death and disability worldwide, and it often results in depression, anxiety, stress, and cognitive impairment in survivors. There is a lack of community-based cognitive interventions for stroke survivors. This pilot single trial aimed to assess the feasibility, acceptability, and perceived effectiveness of a community-based cognitive intervention program called Train-Your-Brain (TYB) for stroke survivors and caregivers. The study focused on improvements in emotional and psychological well-being, as well as cognitive functioning. Methods: A quasi-experimental design was used in this study. A total of 48 participants were recruited and assessed using Depression, Anxiety, Stress Scale - 21 items (DASS-21), Montreal Cognitive Assessment (MoCA) and Symbol Digits Modality Test (SDMT) before and after the intervention. The TYB program consisted of nine sessions and was conducted via the Zoom software application. Participants provided feedback on the program, highlighting areas for improvement. Results: Twenty-seven stroke survivors and 21 caregivers completed the program. Participants expressed high satisfaction with the TYB program but recommended avoiding assessments in December and customizing the program for stroke survivors and caregivers. Stroke survivors showed significant improvements in depression and stress scores, while caregivers experienced no significant improvements after the program. While there was a slight improvement in stroke survivors' cognitive scores after the program, it was not statistically significant. Caregivers, however, experienced a significant decline in cognitive scores. Discussion: The TYB program provided group support and validation, resulting in improved mood and reduced stress among stroke survivors. Cultural collectivism played a significant role in fostering group cohesion. However, the program's limited focus on caregivers and timing of assessments during the December holidays may have affected the outcomes. The TYB program demonstrated feasibility and potential effectiveness in alleviating psychological distress and enhancing cognitive function among stroke survivors. Future research should explore long-term effects, larger sample sizes, and non-English-speaking populations to enhance generalizability. Tailored interventions for caregivers are necessary.

Exploring how brain health strategy training informs the future of work.

Introduction: The workplace typically affords one of the longest periods for continued brain health growth. Brain health is defined by the World Health Organization (WHO) as the promotion of optimal brain development, cognitive health, and well-being across the life course, which we expanded to also include connectedness to people and purpose. This work was motivated by prior work showing individuals, outside of an aggregate setting, benefitted from training as measured by significant performance gains on a holistic BrainHealth Index and its factors (i.e., clarity, connectedness, emotional balance). The current research was conducted during the changing remote work practices emerging post-pandemic to test whether a capacity-building training would be associated with significant gains on measures of brain health and components of burnout. The study also tested the influence of utilization of training modules and days in office for individuals to inform workplace practices. Methods: We investigated whether 193 individuals across a firm's sites would improve on measures of brain health and burnout from micro-delivery of online tactical brain health strategies, combined with two individualized coaching sessions, and practical exercises related to work and personal life, over a six-month period. Brain health was measured using an evidenced-based measure (BrainHealth™ Index) with its components (clarity, connectedness, emotional balance) consistent with the WHO definition. Burnout was measured using the Maslach Burnout Inventory Human Services Survey. Days in office were determined by access to digital workplace applications from the firm's network. Regression analyses were used to assess relationships between change in BrainHealth factors and change in components of the Maslach Burnout Inventory. Results: Results at posttest indicated that 75% of the individuals showed gains on a composite BrainHealth Index and across all three composite factors contributing to brain health. Benefits were directly tied to training utilization such that those who completed the core modules showed the greatest gains. The current results also found an association between gains on both the connectedness and emotional balance brain health factors and reduced on burnout components of occupational exhaustion and depersonalization towards one's workplace. We found that fewer days in the office were associated with greater gains in the clarity factor, but not for connectedness and emotional balance. Discussion: These results support the value of a proactive, capacity-building training to benefit all employees to complement the more widespread limited offerings that address a smaller segment who need mental illness assistance programs. The future of work may be informed by corporate investment in focused efforts to boost collective brain capital through a human-centered, capacity-building approach. Efforts are underway to uncover the value of better brain health, i.e., Brainomics© - which includes economic, societal, and individual benefits.

The potential competency outcome of vigorous brain training game in the elderly: A systematic review.

Background and Aims: The potential outcomes of vigorous brain training game in the elderly is questionable. Methods: A systematic review of studies reporting the outcomes of brain training game under the PRISMA guideline was conducted using the PubMed database (1997-2022). The selection criteria were clinical studies published in English language. Results: A total of 174 articles were identified by searching keywords. However, after screening the relation of the topic and methodology, 21 articles were included. The results of all studies showed positive outcomes after using the brain training game. Variation in the measurement tools were observed. Conclusion: The brain training game showed a positive effect on the brain function. However, the confirmation studies with large populations and standard measurement tools are required for more validated results.

A Real-World Data Study on the Impact of the ReadRx Cognitive Training and Reading Intervention on Cognition, Basic Reading Ability, and Psychosocial Skills for 3527 Children.

Background: The state of reading proficiency among children in the United States continues to be a subject of concern among psychologists, teachers, parents, policy makers, and the education community at large. Despite the widespread use of curricular methods that teach basic reading skills, there remains a large percentage of children that struggle to read. Therefore, novel approaches to reading remediation should be explored. Purpose: The aims of this study were to examine 1) the effect of a multicomponent cognitive and reading intervention on cognitive and reading skills; 2) the role of ADHD, age, sex, IQ score, and individual cognitive skills on the effectiveness of the ReadRx intervention; and 3) parent-reported behavioral outcomes following the ReadRx intervention. Methods: The current study analyzed a large real-world dataset to examine cognitive, reading, and behavioral outcomes for struggling readers (n = 3527) who had completed 24 weeks (120 hours) of intense cognitive training integrated with a structured literacy intervention using ReadRx in a one-on-one clinic setting. Results: Analyses of pretest and post-test scores showed statistically significant changes on all cognitive and reading measures including attention, visual processing, processing speed, long-term memory, working memory, reasoning, phonological awareness, Work Attack, phonetic coding, spelling, comprehension, and overall IQ score with medium to very large effect sizes. The results included an average 4.1-year gain in reading skills including a 6-year gain in phonological awareness. No differences were found based on age, sex, or ADHD status, and minimal differences were found based on pre-intervention IQ score and cognitive test scores. The study also included a qualitative thematic analysis of parent-reported behavioral outcomes revealing themes of improved cognition, academic performance, and psychosocial skills including confidence and perseverance. Conclusion: Our findings were consistent with previous controlled studies on this intervention and offer an encouraging alternative instructional approach to reading remediation that aligns with the Science of Reading and includes intensive remediation of underlying cognitive skills.

Cognitive Computerized Training for Older Adults and Patients with Neurological Disorders: Do the Amount and Training Modality Count? An Umbrella Meta-Regression Analysis.

Numerous applications have been created to train cognition and challenge the brain, a process known as computerized cognitive training (CCT). Despite potential positive results, important questions remain unresolved: the appropriate training duration, the efficacy of CCT depending on its type (commercial or developed in-house for the rehabilitation of specific patients) and delivery mode (at-home or on-site), and the patients most likely to benefit such intervention. This study aims to perform an umbrella meta-analysis and meta-regression to determine if the type of CCT, the delivery mode, the amount of training, and participants' age at inclusion influence the improvement of the cognitive function. To do so, we performed a umbrella meta-analysis. One hundred studies were included in this analysis representing 6407 participants. Statistical improvements were found for the different conditions after the training. We do not find statistical difference between the type of intervention or the delivery mode. No dose-response relationship between the total amount of training and the improvement of cognitive functions was found. CCT is effective in improving cognitive function in patients suffering from neurological conditions and in healthy aging. There is therefore an urgent need for health care systems to recognize its therapeutic potential and to evaluate at a larger scale their integration into the clinical pipeline as preventive and rehabilitation tool.

Behaviour Change Techniques in Computerized Cognitive Training for Cognitively Healthy Older Adults: A Systematic Review.

We aimed to describe behaviour change techniques (BCT) used in trials evaluating computerised cognitive training (CCT) in cognitively healthy older adults, and explore whether BCTs are associated with improved adherence and efficacy. The 90 papers included in a recent meta-analysis were reviewed for information about adherence and use of BCTs in accordance with the Behaviour Change Taxonomy. Studies using a specific BCT were compared with studies not using that BCT on efficacy (difference in Hedges' g [Δg]) using three level meta-regression models and on median adherence using the Wilcoxon test. The median number of BCTs per study was 3 (interquartile range [IQR] = 2-5). 'Feedback on behaviour' (if provided by a person; Δg = -0.19, 95% confidence interval [CI] = -0.31;-0.07) and 'non-specific reward' (Δg = -0.19, CI = -0.34;-0.05) were associated with lower efficacy. Certain BCTs that involve personal contact may be beneficial, although none were statistically significantly associated with greater efficacy. The median percentage of adherence was 90% (IQR = 81-95). Adherence was higher in studies using the BCT 'self-monitoring of behaviour' and lower in studies using the BCT 'graded tasks' than studies not using these BCTs (p < 0.001). These findings provide first evidence that BCTs can influence both adherence to and efficacy of CCT programs in cognitively healthy older adults.

Infra-low frequency neurofeedback in application to Tourette syndrome and other tic disorders: A clinical case series.

We describe our clinical experience in treating patients with Tourette syndrome and other tic disorders using infra-low frequency neurofeedback (ILF NF), often in conjunction with cognitive behavior therapy. Following a narrative description of our approach, we present outcome data for 100 successive cases. Many of the children and adolescents that we have treated since 2005 did not derive sufficient benefit from standard treatment for Tourette syndrome and other tic disorders. In our clinical experience, based on extensive before- and after- testing and symptom tracking, this patient group derived significant additive benefit from complementary neurofeedback treatment. The majority of trainees attained a higher level of functioning and were able to live up to their potential in a way they were not able to prior to neurofeedback treatment.

A Conceptual View of Cognitive Intervention in Older Adults With and Without Cognitive Decline-A Systemic Review.

Background: Dementia is the one of the most common and prominent disease in the elderly person that results in the Cognitive interventions. In this study, we aim to conceptualize the cognitive intervention for older adults with and without cognitive dysfunction and to clarify the heterogeneity existing in this literature field by determining the main variables implicated. Methods: We conducted a study analysis using previous literature highlighting the significant data reporting empirical results from cognitive intervention for healthy older adults and other seniors with different types of dementia. Each paper was reviewed in terms of compensatory cognitive training, cognitive remediation, enrichment, cognitive activation, brain training, cognitive stimulation, cognitive training, and cognitive rehabilitation. The research analysis was performed following rigorous inclusion and exclusion criteria with the purpose of collecting relevant answers to our research questions. Results: We included a total of 168 studies in our review. Our findings indicated heterogeneity regarding methods, concepts, and procedures. Additionally, the values were integrated using different information existing in this field. Conclusion: In conclusion, we highlighted that this is the first review that clarify the discrepancy of various existing definitions, methods, and procedures, as well as the overlapping information in the cognitive interventions.

Does Virtual Reality Feedback at Infra-Low Frequency Improve Centralized Pain With Comorbid Insomnia While Mitigating Risks for Sedative Use Disorder?: A Case Report.

This case report concerns a patient with clinically diagnosed moderate-severe insomnia secondary to chronic lower back pain and sciatica, previously treated with hydrocodone, naproxen, cyclobenzaprine and nightly diazepam. He underwent a trial of 20 sessions of virtual reality neurofeedback therapy (VR-NFB) at infra-low frequency, and by the end of 20 sessions achieved sustained analgesia and consequently, a complete resolution of his pain-related insomnia. Follow-up at 1 year confirmed his improvements were sustained, and he maintained his abstinence from sedatives, as observed on the Prescription Monitoring Program for controlled substances. This case highlights the importance of understanding chronic pain and its connection with restorative sleep: incorporating endogenous neuromodulation in behavioral sleep medicine helped to diminish the risk of benzodiazepine use disorder. This may be the first case of complete resolution of chronic pain with comorbid insomnia after treatment with VR-NFB at the infra-low frequency.

Use of Novel Concussion Protocol With Infralow Frequency Neuromodulation Demonstrates Significant Treatment Response in Patients With Persistent Postconcussion Symptoms, a Retrospective Study.

Introduction: Concussion is a growing public health concern. No uniformly established therapy exists; neurofeedback studies report treatment value. We use infralow frequency neuromodulation (ILF) to remediate disabling neurological symptoms caused by traumatic brain injury (TBI) and noted improved outcomes with a novel concussion protocol. Postconcussion symptoms (PCS) and persistent postconcussion symptoms (PPCS; >3 months post head injury) are designated timelines for protracted neurological complaints following TBI. We performed a retrospective study to explore effectiveness of ILF in PCS/PPCS and investigated the value of using this concussion protocol. Method: Patients with PCS/PPCS seen for their first neurology office visit or received their first neurofeedback session between 1 August 2018 and 31 January 2021 were entered. Outcomes were compared following treatment as usual (TAU) vs. TAU with ILF neurotherapy (TAU+ILF). The study cohort was limited to PPCS patients; the TAU+ILF group was restricted further to PPCS patients receiving at least 10 neurotherapy sessions. Within the TAU+ILF group, comparisons were made between those who trained at least 10 sessions using concussion protocol (TAU+ILF+CP) and those who trained for at least 10 sessions of ILF regardless of protocol (TAU+ILF-CP). Results: Among our resultant PPCS cohort (n = 59) leading persistent neurological complaints were headache (67.8%), memory impairment (57.6%), and brain fog (50.8%). PPCS patients in TAU+ILF+CP (n = 25) demonstrated greater net (p = 0.004) and percent (p = 0.026) improvement of symptoms compared to PPCS subjects in TAU (n = 26). PPCS patients in TAU+ILF-CP (n = 8) trended toward significant symptom improvements compared to TAU, and TAU+ILF+CP trended toward greater efficacy than TAU+ILF-CP. Conclusion: PPCS patients who received TAU+ILF+CP demonstrated significantly greater improvement as a group when compared to TAU. When used as an integrative modality to treatment as usual in managing patients with PPCS, ILF neuromodulation with use of concussion protocol provided significant symptom improvements.

The Cognition and Flow Study (CogFlowS): A Mixed Method Evaluation of a Randomized Feasibility Trial of Cognitive Training in Dementia.

BACKGROUND: Cognitive training (CT) may be beneficial in delaying the onset or slowing dementia progression. CT has been evaluated quantitatively and qualitatively, but none have used mixed methods approaches. OBJECTIVE: The aim of this study was to use a mixed methods approach to identify those who may selectively benefit from CT. METHODS: This was an explanatory sequential mixed methods study involving a quantitative randomized trial of 12 weeks multi-domain CT in healthy older adults (HC, n = 20), and people living with mild cognitive impairment (MCI; n = 12) and dementia (n = 24). Quantitative outcomes included: cognition, mood, quality of life, and activities of daily living. 28 (10 HC, 6 MCI, 12 dementia) training participants completed semi-structured interviews with their carer. Quantitative and qualitative data were integrated using joint displays. RESULTS: Three participants dropped out from the training early-on, leaving 25 participants with follow-up data for full integration (10 HC, 6 MCI, 9 dementia). Dropouts and lower adherence to training were more common in dementia participants with greater non-modifiable barriers. High adherers were more resilient to negative emotions, and poorer or fluctuating performance. Integrated analysis found the majority of participants (n = 24) benefited across outcomes, with no clear profile of individuals who benefited more than others. Participants made a number of key recommendations to improve adherence and minimize dropout to CT. CONCLUSION: Reasons for dropout and low adherence were identified, with recommendations provided for the design of CT for dementia. An individual approach to training should be adopted and low adherence should not preclude engagement with CT.

Development and Co-design of NeuroOrb: A Novel "Serious Gaming" System Targeting Cognitive Impairment in Parkinson's Disease.

Whilst Parkinson's disease (PD) is typically thought of as a motor disease, a significant number of individuals also experience cognitive impairment (CI), ranging from mild-CI to dementia. One technique that may prove effective in delaying the onset of CI in PD is cognitive training (CT); however, evidence to date is variable. This may be due to the implementation of CT in this population, with the motor impairments of PD potentially hampering the ability to use standard equipment, such as pen-and-paper or a computer mouse. This may, in turn, promote negative attitudes toward the CT paradigm, which may correlate with poorer outcomes. Consequently, optimizing a system for the delivery of CT in the PD population may improve the accessibility of and engagement with the CT paradigm, subsequently leading to better outcomes. To achieve this, the NeuroOrb Gaming System was designed, coupling a novel accessible controller, specifically developed for use with people with motor impairments, with a "Serious Games" software suite, custom-designed to target the cognitive domains typically affected in PD. The aim of the current study was to evaluate the usability of the NeuroOrb through a reiterative co-design process, in order to optimize the system for future use in clinical trials of CT in individuals with PD. Individuals with PD (n = 13; mean age = 68.15 years; mean disease duration = 8 years) were recruited from the community and participated in three co-design loops. After implementation of key stakeholder feedback to make significant modifications to the system, system usability was improved and participant attitudes toward the NeuroOrb were very positive. Taken together, this provides rationale for moving forward with a future clinical trial investigating the utility of the NeuroOrb as a tool to deliver CT in PD.

The promise of low-tech intervention in a high-tech era: Remodeling pathological brain circuits using behavioral reverse engineering.

As an academic pursuit, neuroscience is enjoying a golden age. From a clinical perspective, our field is failing. Conventional 20th century drugs and devices are not well-matched to the heterogeneity, scale, and connectivity of neural circuits that produce aberrant mental states and behavior. Laboratory-based methods for editing neural genomes and sculpting activity patterns are exciting, but their applications for hundreds of millions of people with mental health disorders is uncertain. We argue that mechanisms for regulating adult brain plasticity and remodeling pathological activity are substantially pre-wired, and we suggest new minimally invasive strategies to harness and direct these endogenous systems. Drawing from studies across the neuroscience literature, we describe approaches that identify neural biomarkers more closely linked to upstream causes-rather than downstream consequences-of disordered behavioral states. We highlight the potential for innovation and discovery in reverse engineering approaches that refine bespoke behavioral "agonists" to drive upstream neural biomarkers in normative directions and reduce clinical symptoms for select classes of neuropsychiatric disorders.