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With the limited capacity for self-repair in the adult CNS, efforts to stimulate quiescent stem cell populations within discrete brain regions, as well as harness the potential of stem cell transplants, offer significant hope for neural repair. These new cells are capable of providing trophic cues to support residual host populations and/or replace those cells lost to the primary insult. However, issues with low-level adult neurogenesis, cell survival, directed differentiation and inadequate reinnervation of host tissue have impeded the full potential of these therapeutic approaches and their clinical advancement. Biomaterials offer novel approaches to stimulate endogenous neurogenesis, as well as for the delivery and support of neural progenitor transplants, providing a tissue-appropriate physical and trophic milieu for the newly integrating cells. In this review, we will discuss the various approaches by which bioengineered scaffolds may improve stem cell-based therapies for repair of the CNS. [ABSTRACT FROM AUTHOR]

Intergenerational relationships have been established as a critical locus of psychosocial development, meeting needs of identity development for youth, generativity for elders, and connection and belonging for both. However, intergenerational relationships are both rare in the LGBTQ+ community and sorely needed as a buffer to the discrimination and harm that those within the community experience from systemic and structural oppression. Focusing on sexual identity, and employing a letter writing paradigm, we investigated the content of wisdom that LGB elders have to share with youth. In a descriptive, exploratory, mixed-methods, and pre-registered study, 94 adults ranging in age 50 to 79 years ( M  = 55.98; SD  = 6.30) wrote letters to a fictional youth, Sam, as well as completed surveys of psychosocial development and well-being. Letters were content coded for themes, as well as for emotional tone and subjective perspective. The most common themes of wisdom shared included knowing and celebrating oneself, negotiating an oppressive society, and finding one's community. Those who wrote more emotionally positive letters scored higher on measures of wisdom and generativity, and lower on embitterment. Results are discussed in terms of the importance of cultivating opportunities for wisdom-sharing within LGBTQ+ communities to promote flourishing across the lifespan.

Objective: Few studies have examined the interplay between collective trauma (e.g., the COVID-19 pandemic) and personal trauma (e.g., child abuse and discrimination). In a longitudinal child maltreatment study, with a community sample added, negative COVID impact (e.g., financial and mental health difficulties due to COVID) was examined in relation to childhood abuse exposure and perceived discrimination., Method: Adults ( N = 135) completed an online survey about trauma- and pandemic-related experiences. Regressions examined predictors of negative COVID impact and posttraumatic stress disorder (PTSD) symptoms during the pandemic., Results: Although cumulative maltreatment contributed to negative COVID impact, when high levels of cumulative maltreatment had been experienced in childhood, greater negative COVID impact did not significantly relate to PTSD symptoms: For these participants, PTSD symptoms were relatively high (but not at ceiling) in adulthood overall. Negative COVID impact predicted PTSD symptoms only at low levels of cumulative child abuse. Perceived discrimination was associated with negative COVID impact and PTSD symptomatology., Conclusions: Cumulative childhood abuse at high levels likely set the stage for PTSD symptoms in adulthood, regardless of negative COVID impact. Individuals with lower levels of cumulative childhood abuse had fewer PTSD symptoms unless COVID had a stronger negative impact on their lives. Discrimination contributed to lower pandemic-related well-being. Insight is provided into special vulnerabilities associated with maltreatment backgrounds and discrimination at times of collective challenges. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

The central nervous system's limited capacity for regeneration often leads to permanent neuronal loss following injury. Reprogramming resident reactive astrocytes into induced neurons at the site of injury is a promising strategy for neural repair, but challenges persist in stabilizing and accurately targeting viral vectors for transgene expression. In this study, we employed a bioinspired self-assembling peptide (SAP) hydrogel for the precise and controlled release of a hybrid adeno-associated virus (AAV) vector, AAVDJ, carrying the NeuroD1 neural reprogramming transgene. This method effectively mitigates the issues of high viral dosage at the target site, off-target delivery, and immunogenic reactions, enhancing the vector's targeting and reprogramming efficiency. In vitro , this vector successfully induced neuron formation, as confirmed by morphological, histochemical, and electrophysiological analyses. In vivo , SAP-mediated delivery of AAVDJ-NeuroD1 facilitated the trans-differentiation of reactive host astrocytes into induced neurons, concurrently reducing glial scarring. Our findings introduce a safe and effective method for treating central nervous system injuries, marking a significant advancement in regenerative neuroscience.

Inhibitory neurons originating from the ventral forebrain are associated with several neurological conditions. Distinct ventral forebrain subpopulations are generated from topographically defined zones; lateral-, medial- and caudal ganglionic eminences (LGE, MGE and CGE), yet key specification factors often span across developing zones contributing to difficulty in defining unique LGE, MGE or CGE profiles. Here we use human pluripotent stem cell (hPSC) reporter lines (NKX2.1-GFP and MEIS2-mCherry) and manipulation of morphogen gradients to gain greater insight into regional specification of these distinct zones. We identified Sonic hedgehog (SHH)-WNT crosstalk in regulating LGE and MGE fate and uncovered a role for retinoic acid signaling in CGE development. Unraveling the influence of these signaling pathways permitted development of fully defined protocols that favored generation of the three GE domains. These findings provide insight into the context-dependent role of morphogens in human GE specification and are of value for in vitro disease modeling and advancement of new therapies., Competing Interests: Conflict of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Direct-acting antivirals are needed to combat coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). The papain-like protease (PLpro) domain of Nsp3 from SARS-CoV-2 is essential for viral replication. In addition, PLpro dysregulates the host immune response by cleaving ubiquitin and interferon-stimulated gene 15 protein (ISG15) from host proteins. As a result, PLpro is a promising target for inhibition by small-molecule therapeutics. Here we have designed a series of covalent inhibitors by introducing a peptidomimetic linker and reactive electrophile onto analogs of the noncovalent PLpro inhibitor GRL0617. The most potent compound inhibited PLpro with k inact /K I = 10,000 M - 1 s - 1 , achieved sub-µM EC 50 values against three SARS-CoV-2 variants in mammalian cell lines, and did not inhibit a panel of human deubiquitinases at > 30 µM concentrations of inhibitor. An X-ray co-crystal structure of the compound bound to PLpro validated our design strategy and established the molecular basis for covalent inhibition and selectivity against structurally similar human DUBs. These findings present an opportunity for further development of covalent PLpro inhibitors.

Midbrain dopaminergic (DA) neurons include many subtypes characterized by their location, connectivity and function. Surprisingly, mechanisms underpinning the specification of A9 neurons [responsible for motor function, including within ventral midbrain (VM) grafts for treating Parkinson's disease (PD)] over adjacent A10, remains largely speculated. We assessed the impact of synaptic targeting on survival, integration, and phenotype acquisition of dopaminergic neurons within VM grafts generated from fetal tissue or human pluripotent stem cells (PSCs). VM progenitors were grafted into female mice with 6OHDA-lesions of host midbrain dopamine neurons, with some animals also receiving intrastriatal quinolinic acid (QA) injections to ablate medium spiny neurons (MSN), the A9 neuron primary target. While loss of MSNs variably affected graft survival, it significantly reduced striatal yet increased cortical innervation. Consequently, grafts showed reduced A9 and increased A10 specification, with more DA neurons failing to mature into either subtype. These findings highlight the importance of target acquisition on DA subtype specification during development and repair. SIGNIFICANCE STATEMENT Parish and colleagues highlight, in a rodent model of Parkinson's disease (PD), the importance of synaptic target acquisition in the survival, integration and phenotypic specification of grafted dopamine neurons derived from fetal tissue and human stem cells. Ablation of host striatal neurons resulted in reduced dopamine neuron survival within grafts, re-routing of dopamine fibers from striatal to alternate cortical targets and a consequential reduced specification of A9 dopamine neurons (the subpopulation critical for restoration of motor function) and increase in A10 DA neurons., (Copyright © 2022 the authors.)

Clinical studies have provided evidence for dopamine (DA) cell replacement therapy in Parkinson's Disease. However, grafts derived from foetal tissue or pluripotent stem cells (PSCs) remain heterogeneous, with a high proportion of non-dopaminergic cells, and display subthreshold reinnervation of target tissues, thereby highlighting the need to identify new strategies to improve graft outcomes. In recent work, Stromal Cell-Derived Factor-1 (SDF1), secreted from meninges, has been shown to exert many roles during ventral midbrain DA development and DA-directed differentiation of PSCs. Related, co-implantation of meningeal cells has been shown to improve neural graft outcomes, however, no direct evidence for the role of SDF1 in neural grafting has been shown. Due to the rapid degradation of SDF1 protein, here, we utilised a hydrogel to entrap the protein and sustain its delivery at the transplant site to assess the impact on DA progenitor differentiation, survival and plasticity. Hydrogels were fabricated from self-assembling peptides (SAP), presenting an epitope for laminin, the brain's main extracellular matrix protein, thereby providing cell adhesive support for the grafts and additional laminin-integrin signalling to influence cell fate. We show that SDF1 functionalised SAP hydrogels resulted in larger grafts, containing more DA neurons, increased A9 DA specification (the subpopulation of DA neurons responsible for motor function) and enhanced innervation. These findings demonstrate the capacity for functionalised, tissue-specific hydrogels to improve the composition of grafts targeted for neural repair.

Midbrain dopamine (mDA) neurons can be replaced in patients with Parkinson's disease (PD) in order to provide long-term improvement in motor functions. The limited capacity for long-distance axonal growth in the adult brain means that cells are transplanted ectopically, into the striatal target. As a consequence, several mDA pathways are not re-instated, which may underlie the incomplete restoration of motor function in patients. Here, we show that viral delivery of GDNF to the striatum, in conjunction with homotopic transplantation of human pluripotent stem-cell-derived mDA neurons, recapitulates brain-wide mDA target innervation. The grafts provided re-instatement of striatal dopamine levels and correction of motor function and also connectivity with additional mDA target nuclei not well innervated by ectopic grafts. These results demonstrate the remarkable capacity for achieving functional and anatomically precise reconstruction of long-distance circuitry in the adult brain by matching appropriate growth-factor signaling to grafting of specific cell types., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

In cell replacement approaches for Parkinson's disease, the intracerebral implantation of dopamine neuron-rich grafts generates a neuroinflammatory response to the grafted cells that contributes to its varied outcome. Thus, the aim of the present study was to fabricate an anti-inflammatory cytokine-eluting collagen hydrogel capable of delivering interleukin (IL)-10 to the brain for reduction of the neuroinflammatory response to intracerebral cellular grafts. In vitro assessment revealed that cross-linker concentration affected the microstructure and gelation kinetics of the hydrogels and their IL-10 elution kinetics, but not their cytocompatibility or the functionality of the eluted IL-10. In vivo evaluation revealed that the hydrogels were capable of delivering and retaining IL-10 in the rat striatum, and reducing the neuroinflammatory (microglial) response to hydrogel-encapsulated grafts. In conclusion, IL-10-eluting collagen hydrogels may have beneficial anti-inflammatory effects in the context of cellular brain repair therapies for Parkinson's disease and should be investigated further., Competing Interests: The authors declare that there are no competing interests associated with the manuscript., (© 2021 The Author(s).)

Soluble low-molecular-weight oligomers formed during the early aggregation of amyloid peptides have been hypothesized as a major toxic species of amyloidogenesis. Herein, we performed the first synergic in silico , in vitro and in vivo validations of the structure, dynamics and toxicity of Aβ42 oligomers. Aβ peptides readily assembled into β-rich oligomers comprised of extended β-hairpins and β-strands. Nanosized β-barrels were observed with certainty with simulations, transmission electron microscopy and Fourier transform infrared spectroscopy, corroborated by immunohistochemistry, cell viability, apoptosis, inflammation, autophagy and animal behavior assays. Secondary and tertiary structural proprieties of these oligomers, such as the sequence regions with high β-sheet propensities and inter-residue contact frequency patterns, were similar to the properties known for Aβ fibrils. The unambiguous spontaneous formation of β-barrels in the early aggregation of Aβ42 supports their roles as the common toxic intermediates in Alzheimer's pathobiology and a target for Alzheimer's therapeutics., Competing Interests: Conflicts of interest There are no conflicts to declare.

Despite advancements in human pluripotent stem cells (hPSCs) differentiation protocols to generate appropriate neuronal progenitors suitable for transplantation in Parkinson's disease, resultant grafts contain low proportions of dopamine neurons. Added to this is the tumorigenic risk associated with the potential presence of incompletely patterned, proliferative cells within grafts. Here, we utilised a hPSC line carrying a FailSafe TM suicide gene (thymidine kinase linked to cyclinD1) to selectively ablate proliferative cells in order to improve safety and purity of neural transplantation in a Parkinsonian model. The engineered FailSafe TM hPSCs demonstrated robust ventral midbrain specification in vitro, capable of forming neural grafts upon transplantation. Activation of the suicide gene within weeks after transplantation, by ganciclovir administration, resulted in significantly smaller grafts without affecting the total yield of dopamine neurons, their capacity to innervate the host brain or reverse motor deficits at six months in a rat Parkinsonian model. Within ganciclovir-treated grafts, other neuronal, glial and non-neural populations (including proliferative cells), were significantly reduced-cell types that may pose adverse or unknown influences on graft and host function. These findings demonstrate the capacity of a suicide gene-based system to improve both the standardisation and safety of hPSC-derived grafts in a rat model of Parkinsonism.

Background/objectives: Though maculopapular cutaneous mastocytosis is the most common form of pediatric mastocytosis, it remains unclear which patients will experience severe symptoms. We sought to better define the presentation and the cutaneous and systemic signs and symptoms in patients with maculopapular cutaneous mastocytosis., Methods: We analyzed retrospective data on 227 patients diagnosed with maculopapular cutaneous mastocytosis prior to age 15 years from five US clinical sites. We collected data on signs, symptoms, age of onset, and laboratory testing., Results: Median age of onset of maculopapular cutaneous mastocytosis was 3 months, with 94% of patients presenting prior to age 2 (range 0-15 years). Patients presenting before age 2 had significantly lower serum tryptase level (P = .019). Greater number of skin lesions (P = .006), number of reported skin signs and symptoms (P < .001), and higher tryptase levels (P < .001) were associated with more systemic symptoms., Conclusion: Children with maculopapular cutaneous mastocytosis, who have greater skin involvement, higher serum tryptase level, and more skin signs and symptoms, are more likely to have systemic symptoms., (© 2020 Wiley Periodicals LLC.)

Objective: We present a case of a 22-year-old bodybuilder diagnosed with myocarditis secondary to clenbuterol use., Results: The patient was primarily managed conservatively by the discontinuation of clenbuterol and the temporary use of dual anti-platelets, beta-blockers and nitrates., Conclusion: Clenbuterol is a long-acting beta-2 agonist primarily used in veterinary medicine. In recent years, it has been illegally marketed as a weight loss supplement because of its anabolic properties and is popular among fitness enthusiasts. It is our aim to use this case to underscore the adverse effects of this drug with hopes that tighter regulations will be instituted to stem its illegal distribution., Learning Points: Clenbuterol is primarily a veterinary drug with bronchodilator and tocolytic properties.It is illegally used as a performance enhancer by athletes and bodybuilders because of its anabolic properties.Clenbuterol misuse can result in myocardial injury., Competing Interests: Conflicts of Interests: The Authors declare that there are no competing interests., (© EFIM 2020.)

Objective: We present a patient with pancreatic cancer who developed weakness, acute renal failure and significantly raised creatine kinase levels post-ERCP and who was assessed as having contrast-induced rhabdomyolysis., Results: The patient underwent haemofiltration and ultimately succumbed to his condition., Conclusion: Rhabdomyolysis is a potentially life-threatening condition which occurs because of damage to skeletal muscle, with release of myoglobin and electrolytes into the circulation. The mortality rate is 59% in severe cases, despite appropriate treatment., Learning Points: Iodine-based contrast can cause rhabdomyolysis by reducing blood flow to the muscle.Renal replacement therapy does not improve the mortality rate of rhabdomyolysis.<10% of patients present with the classic triad of myalgia, muscle weakness and tea-coloured urine; creatine kinase levels greater than 5 times the upper limit of normal are the gold standard for diagnosing rhabdomyolysis that is not related to statin use., Competing Interests: Conflicts of Interests: The Authors declare that there are no competing interests., (© EFIM 2020.)

Dopaminergic neurons (DAns), generated from human pluripotent stem cells (hPSCs), are capable of functionally integrating following transplantation and have recently advanced to clinical trials for Parkinson's disease (PD). However, pre-clinical studies have highlighted the low proportion of DAns within hPSC-derived grafts and their inferior plasticity compared to fetal tissue. Here, we examined whether delivery of a developmentally critical protein, glial cell line-derived neurotrophic factor (GDNF), could improve graft outcomes. We tracked the response of DAns implanted into either a GDNF-rich environment or after a delay in exposure. Early GDNF promoted survival and plasticity of non-DAns, leading to enhanced motor recovery in PD rats. Delayed exposure to GDNF promoted functional recovery through increases in DAn specification, DAn plasticity, and DA metabolism. Transcriptional profiling revealed a role for mitogen-activated protein kinase (MAPK)-signaling downstream of GDNF. Collectively, these results demonstrate the potential of neurotrophic gene therapy strategies to improve hPSC graft outcomes., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Delusional infestation is a psychiatric condition defined by a fixed belief of infestation despite contrary evidence. Diagnosis includes exclusion of organic etiologies. Treatment with antipsychotics is effective and safe in the majority of patients. Patients are characteristically reluctant to pursue psychiatric evaluation and may resist discussing their disease in psychiatric terms. Strategies to strengthen the provider-patient therapeutic alliance facilitate communication around appropriate treatment. Without antipsychotic medications, patients can become heavy utilizers of care and practice self-destructive behaviors in attempts to clear their perceived infestation., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The aim of this case report and literature review is to explore the rarely highlighted co-occurrence of malignant melanoma and Parkinson's disease (PD) and to describe the devastating effects on those affected. We present a case of acute confusion and worsening shuffling gait in a patient with Parkinson's disease who eventually succumbed to metastatic malignant melanoma, secondary to a primary malignant melanoma on the back that was treated 6 years earlier. More research is needed to better characterize the associations between these two conditions, and to evaluate the effectiveness of prevention strategies such as melanoma screening for adults with PD., Learning Points: The underlying mechanism for the co-occurrence of Parkinson's disease (PD) and malignant melanoma remains unclear but available evidence suggests genetic associations and environmental factors as potential causes.Patients with PD may require closer dermatological surveillance, particularly those with other risk factors for melanoma such as prolonged sun exposure.More research is needed to better characterize the associations between PD and skin cancers, and to evaluate the effectiveness of prevention strategies such as melanoma screening for adults with PD., Competing Interests: Conflicts of Interests: The Authors declare that there are no competing interest, (© EFIM 2019.)

Evidence is accumulating to suggest that viral infections and consequent viral-mediated neuroinflammation may contribute to the etiology of idiopathic Parkinson's disease. Moreover, viruses have been shown to influence α-synuclein oligomerization as well as the autophagic clearance of abnormal intra-cellular proteins aggregations, both of which are key neuropathological events in Parkinson's disease pathogenesis. To further investigate the interaction between viral-mediated neuroinflammation and α-synuclein aggregation in the context of Parkinson's disease, this study sought to determine the impact of viral neuroinflammatory priming on α-synuclein aggregate-induced neuroinflammation and neurotoxicity in the rat nigrostriatal pathway. To do so, male Sprague-Dawley rats were intra-nigrally injected with a synthetic mimetic of viral dsRNA (poly I:C) followed two weeks later by a peptidomimetic small molecule which accelerates α-synuclein fibril formation (FN075). The impact of the viral priming on α-synuclein aggregation-induced neuroinflammation, neurodegeneration and motor dysfunction was assessed. We found that prior administration of the viral mimetic poly I:C significantly exacerbated or precipitated the α-synuclein aggregate induced neuropathological and behavioral effects. Specifically, sequential exposure to the two challenges caused a significant increase in nigral microgliosis (p < 0.001) and astrocytosis (p < 0.01); precipitated a significant degeneration of the nigrostriatal cell bodies (p < 0.05); and precipitated a significant impairment in forelimb kinesis (p < 0.01) and sensorimotor integration (p < 0.01). The enhanced sensitivity of the nigrostriatal neurons to pathological α-synuclein aggregation after viral neuroinflammatory priming further suggests that viral infections may contribute to the etiology and pathogenesis of Parkinson's disease., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Angioimmunoblastic T-cell lymphoma (AITL) is a rare form of non-Hodgkin lymphoma often accompanied by autoimmune and paraneoplastic phenomena. Up to 50% of patients with AITL present with skin manifestations. This case series highlights two cases of AITL presenting with unusual cutaneous findings: one with a medium-vessel vasculitis and another with a chronic urticarial eruption. Clinicians should consider AITL in the differential diagnosis of vasculitis or urticaria refractory to standard treatment.

The dopamine precursor, levodopa, remains the "gold standard" treatment for Parkinson's disease, and, although it provides superlative efficacy in the early stages of the disease, its long-term use is limited by the development of severe motor side effects and a significant abating of therapeutic efficacy. Therefore, there remains a major unmet clinical need for the development of effective neuroprotective, neurorestorative or neuroreparatory therapies for this condition. The relatively selective loss of dopaminergic neurons from the nigrostriatal pathway makes Parkinson's disease an ideal candidate for reparative cell therapies, wherein the dopaminergic neurons that are lost in the condition are replaced through direct cell transplantation into the brain. To date, this approach has been developed, validated and clinically assessed using dopamine neuron-rich foetal ventral mesencephalon grafts which have been shown to survive and reinnervate the denervated brain after transplantation, and to restore motor function. However, despite long-term symptomatic relief in some patients, significant limitations, including poor graft survival and the impact this has on the number of foetal donors required, have prevented this therapy being more widely adopted as a restorative approach for Parkinson's disease. Injectable biomaterial scaffolds have the potential to improve the delivery, engraftment and survival of these grafts in the brain through provision of a supportive microenvironment for cell adhesion, growth and immune shielding. This article will briefly review the development of primary cell therapies for brain repair in Parkinson's disease and will consider the emerging literature which highlights the potential of using injectable biomaterial hydrogels in this context., (© 2018 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Biomaterials have been shown to significantly improve the outcome of cellular reparative approaches for Parkinson's disease in experimental studies because of their ability to provide transplanted cells with a supportive microenvironment and shielding from the host immune system. However, given that the margin for improvement in such reparative therapies is considerable, further studies are required to fully investigate and harness the potential of biomaterials in this context. Given that several recent studies have demonstrated improved brain repair in Parkinsonian models when using dopaminergic grafts derived from younger foetal donors, we hypothesized that encapsulating these cells in a supportive biomaterial would further improve their reparative efficacy. Thus, this study aimed to determine the impact of a GDNF-loaded collagen hydrogel on the survival, reinnervation, and functional efficacy of dopaminergic neurons derived from young donors. To do so, hemi-Parkinsonian (6-hydroxydopamine-lesioned) rats received intrastriatal transplants of embryonic day 12 cells extracted from the rat ventral mesencephalon either alone, in a collagen hydrogel, with GDNF, or in a GDNF-loaded collagen hydrogel. Methamphetamine-induced rotational behaviour was assessed at three weekly intervals for a total of 12 weeks, after which rats were sacrificed for postmortem assessment of graft survival. We found that, following intrastriatal transplantation to the lesioned striatum, the GDNF-loaded collagen hydrogel significantly increased the survival (4-fold), reinnervation (5.4-fold), and functional efficacy of the embryonic day 12 dopaminergic neurons. In conclusion, this study further demonstrates the significant potential of biomaterial hydrogel scaffolds for cellular brain repair approaches in neurodegenerative diseases such as Parkinson's disease., (© 2018 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Background: It is known that proteins associated with Alzheimer's disease (AD) pathogenesis are significantly reduced by 40 Hz entrainment in mice. If this were to translate to humans, verifying that such a light stimulus can induce a 40 Hz entrainment response in humans and harnessing insights from these case studies could be one step in the development of a multisensory device to prevent and treat AD., Objective: Verify the inducement of a 40 Hz response in the human brain by a 40 Hz light stimulus and obtain insights that could potentially aid in the development of a multisensory device for the prevention and treatment of AD., Methods: Electroencephalographic brain activity was recorded simultaneously with application of stimulus at different frequencies and intensities. Power spectral densities were analyzed., Results: Entrainment to visual stimuli occurred with the largest response at 40 Hz. The high intensity 40 Hz stimulus caused widespread entrainment. The number of electrodes demonstrating entrainment increased with increasing light intensity. Largest amplitudes for the high intensity 40 Hz stimulus were consistently found at the primary visual cortex. There was a harmonic effect at double the frequency for the 40 Hz stimulus. An eyes-open protocol caused more entrainment than an eyes-closed protocol., Conclusion: It was possible to induce widespread entrainment using a 40 Hz light stimulus in this sample cohort. Insights gleaned from these case studies could potentially aid in the development of a multisensory medical device to prevent and treat AD.