Khalil, M. H. (2024). Borderline in a linear city: Urban living brings borderline personality disorder to crisis through neuroplasticity-an urgent call to action. Frontiers in Psychiatry, 15, 1524531.

–

Khalil, M. H. (2024). The BDNF-Interactive Model for Sustainable Hippocampal Neurogenesis in Humans: Synergistic Effects of Environmentally-Mediated Physical Activity, Cognitive Stimulation, and Mindfulness. International Journal of Molecular Sciences. https://doi.org/10.3390/ijms252312924

This paper bridges critical gaps through proposing a novel, environmentally mediated brain-derived neurotrophic factor (BDNF)-interactive model that promises to sustain adult hippocampal neurogenesis in humans. It explains how three environmental enrichment mechanisms (physical activity, cognitive stimulation, and mindfulness) can integratively regulate BDNF and other growth factors and neurotransmitters to support neurogenesis at various stages, and how those mechanisms can be promoted by the physical environment. The approach enables the isolation of specific environmental factors and their molecular effects to promote sustainable BDNF regulation by testing the environment’s ability to increase BDNF immediately or shortly before it is consumed for muscle repair or brain update. This model offers a novel, feasible method to research environment enrichment and neurogenesis dynamics in real-world human contexts at the immediate molecular level, overcoming the confounds of complex environment settings and challenges of long-term exposure and structural plasticity changes. The model promises to advance understanding of environmental influences on the hippocampus to enhance brain health and cognition. This work bridges fundamental gaps in methodology and knowledge to facilitate more research on the enrichment–neuroplasticity interplay for humans without methodological limitations.

–

Khalil, M. H., & Steemers, K. (2024). Housing Environmental Enrichment, Lifestyles, and Public Health Indicators of Neurogenesis in Humans: A Pilot Study. International Journal of Environmental Research and Public Health, 21(12), 1553. https://doi.org/10.3390/ijerph21121553

Background: In response to the rising mental health concerns and cognitive decline associated with the human brain’s neurogenesis, which continues until the tenth decade of life but declines with age and is suppressed by poor environments, this pilot study investigates how physical environments may influence public health proxy measures of neurogenesis in humans. This pilot study focuses on the residential environment where people spend most of their time and age in place, exploring the dependency of depression, anxiety, and cognitive impairment variations on spatial and lifestyle variables. Methods: A total of 142 healthy adults in England completed a survey consisting of PHQ-8, GAD-7, and CFI questionnaires and other questions developed to capture the variance in spatial and lifestyle factors such as time spent at home, house type layout complexity, spaciousness, physical activity, routine and spatial novelty, and perceived loneliness. Results: Extensive time spent at home has adverse effects on all measures, while multi-storey houses perform better than single-story houses with positive correlations with physical activity and spatial novelty. Separate regression models on the variance in depression, as the most salient dependent variable and reliably associated with neurogenesis, reveal that getting out of the house explains 20.5% of the variance in depression symptoms. At the scale of the house, multi-storey houses explain 16.5% of the variance. Both percentages are closer to the effect of loneliness, which we found to explain 26.6% of the variance in depression. Conclusions: The built environment appears to be significantly associated with changes in cognitive function and mental health symptoms associated with neurogenesis. This pilot study shows the equally important effect of physical and social enrichment, offering critically needed insights for neuroarchitecture and brain health research that is interested in public health.

–

Khalil, M. H. (2024). Environmental Affordance for Physical Activity, Neurosustainability, and Brain Health: Quantifying the Built Environment’s Ability to Sustain BDNF Release by Reaching Metabolic Equivalents (METs). Brain Sciences, 14, 1133. https://doi.org/10.3390/brainsci14111133

Background/Objectives: Unlike enriched environments for rodents, human-built environments often hinder neuroplasticity through sedentary lifestyles, to which exercise can merely overcome its adverse effects. This paper introduces “environmental affordance for physical activity” to quantify the potential of spatial layout designs to stimulate activity and sustain neuroplasticity, mainly hippocampal neurogenesis. Methods: A novel framework links metabolic equivalents (METs) that can be afforded by the spatial layout of the built environment to its role in increasing the brain-derived neurotrophic factor (BDNF)—a biomarker that promotes and sustains adult hippocampal neurogenesis and synaptic plasticity. Equations are developed to assess the built environment’s affordance for physical activity through BDNF changes measurable after brief exposure to the built environment for 20–35 min. Results: The developed equations are evidenced to be feasible to cause BDNF release through low- to moderate-intensity physical activity. This model provides a feasible assessment tool to test the built environment’s effectiveness towards neurosustainability. Conclusions: By sustaining neurogenesis, the environmental affordance for physical activity holds promise for improving mental health and preventing cognitive decline.

–

Khalil, M. H. (2024). Neurosustainability. Frontiers in Human Neuroscience. https://doi.org/10.3389/fnhum.2024.1436179

While the human brain has evolved extraordinary abilities to dominate nature, modern living has paradoxically trapped it in a contemporary “cage” that stifles neuroplasticity. Within this modern environment lurk unseen natural laws with power to sustain the human brain’s adaptive capacities – if consciously orchestrated into the environments we design. For too long our contemporary environments have imposed an unyielding static state, while still neglecting the brain’s constant adaptive nature as it evolves to dominate the natural world with increasing sophistication. The theory introduced in this article aims to go back in nature without having to go back in time, introducing and expounding Neurosustainability as a novel paradigm seeing beyond the contemporary confines to architect environments and brains in parallel. Its integrated neuro-evidenced framework proposes four enrichment scopes—spatial, natural, aesthetic, and social—each holding multifaceted attributes promising to sustain regions like the hippocampus, cortex and amygdala. Neurosustainability aims to liberate the quintessential essence of nature to sustain and enhance neuroplastic processes through a cycle that begins with design and extends through epigenetic changes. This paradigm shift aims to foster cognitive health and wellness by addressing issues like stress, depression, anxiety and cognitive decline common in the contemporary era thereby offering a path toward a more neurosustainable era aiming to nurture the evolution of the human brain now and beyond.

–

Khalil, M. H. (2024). Environmental enrichment: a systematic review on the effect of a changing spatial complexity on hippocampal neurogenesis and plasticity in rodents, with considerations for translation to urban and built environments for humans. Frontiers in Neuroscience. https://doi.org/10.3389/fnins.2024.1368411

Hippocampal neurogenesis is critical for improving learning, memory, and spatial navigation. Inhabiting and navigating spatial complexity is key to stimulating adult hippocampal neurogenesis (AHN) in rodents because they share similar hippocampal neuroplasticity characteristics with humans. AHN in humans has recently been found to persist until the tenth decade of life, but it declines with aging and is influenced by environmental enrichment. This systematic review investigated the impact of spatial complexity on neurogenesis and hippocampal plasticity in rodents, and discussed the translatability of these findings to human interventions. Comprehensive searches were conducted on three databases in English: PubMed, Web of Science, and Scopus. All literature published until December 2023 was screened and assessed for eligibility. A total of 32 studies with original data were included, and the process is reported in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement and checklist. The studies evaluated various models of spatial complexity in rodents, including environmental enrichment, changes to in-cage elements, complex layouts, and navigational mazes featuring novelty and intermittent complexity. A regression equation was formulated to synthesize key factors influencing neurogenesis, such as duration, physical activity, frequency of changes, diversity of complexity, age, living space size, and temperature. Findings underscore the cognitive benefits of spatial complexity interventions and inform future translational research from rodents to humans. Home-cage enrichment and models like the Hamlet complex maze and the Marlau cage offer insight into how architectural design and urban navigational complexity can impact neurogenesis in humans. In-space changing complexity, with and without physical activity, is effective for stimulating neurogenesis. While evidence on intermittent spatial complexity in humans is limited, data from the COVID-19 pandemic lockdowns provide preliminary evidence. Existing equations relating rodent and human ages may allow for the translation of enrichment protocol durations from rodents to humans.

–

Khalil, M. H. (2024). From Cave to Cage? The Evolution of Housing Complexity and the Contemporary Dead End for the Human Brain. Housing, Theory and Society. https://doi.org/10.1080/14036096.2024.2393694

The evolution of the ever-changing neuroplastic human brain is inseparably linked to its environment. While early humans evolved in response to nature’s complexity and unpredictability environments, over millennia, the housing trajectory has increasingly prioritized sedentary behaviors, predictability, and comfort at the expense of cognitive stimulation. Modern life stress, mental health issues, and cognitive decline are markers of a poor environment. The pandemic lockdown has implicitly exposed that we need better houses for our brains. This paper goes back in time, navigating the cross-cultural evolution of environmental complexity to escape the contemporary dead end for the human brain that needs to evolve further. The paper advocates for a paradigm shift in housing design, emphasizing the need to foster neuroplasticity rather than constrain it. By reconceptualizing houses as architects of our brains, architecture becomes an independent variable embedding what the brain needs rather than embodying what the brain wants.

–

Khalil, M. H., Kawi, A. A., & Zaky, H. H. (2024). Homes in flux: Evaluating personal and social dynamics amid urban variability and mass-produced prototype housing. Journal of Environmental Psychology, 96, 102321.

Amidst the ever-evolving landscape of global urbanization, this research delves into the profound repercussions of dynamic shifts in residential settings on both personal and social interconnectedness. Focusing on the evo- lution into novel urban constructs and gated enclaves—underscored by the influx of mass-produced prototype houses, with Egypt serving as our representative context of a global phenomenon—we offer a nuanced exami- nation of how these transitions mold individuals’ perceptions of personal and social connectedness. Employing a survey instrument administered to a sample of 298 respondents, encompassing retrospectives on childhood homes alongside present-day residences, our inquiry unveils a multifaceted narrative that enriches the tapestry of environmental psychology scholarship. Contrary to expectations, the advent of new cities appears to wield no significance over personal or social bonds, while gated communities surprisingly exhibit a notable positive significance solely with personal connectedness, with no significant relationship observed for social connect- edness expected from the label of community. Furthermore, apartments and standalone villas prototype typol- ogies manifest divergent impacts on connectedness, defying conventional assumptions. Gender emerges as a pertinent covariate, intricately intertwined with the present-day sense of personal connectedness. These reve- lations underscore the intricate nexus of factors dictating residential connectedness, advocating for a holistic integration of tangled personal, social, and physical attributes in residential urban planning and housing ar- chitecture. Our study advocates for sustained exploration into the intricate mechanisms underpinning the nexus between residential milieus and interpersonal bonds, urging a nuanced understanding of cultural, geographical, and individual nuances to inform interpersonal sustainable paradigm that promotes social interaction and per- sonal well-being.

–

Khalil, M. H. (2024). Fairytale-estate homes, real estate hopes: A framework informing housing decisions in Egypt. Housing Studies, 1-27.

Housing decisions are often constrained by practicality, while dream home aspirations remain unrestrained. This gap widens significantly in the housing industry, where boundaries blur, advertising fairytale-like estates while providing homes closer to reality than dreams. This study researches, proposes, and tests a framework to assist in making informed housing decisions between dreams and reality. Through a set of 24 themes and a three-step funnel, this paper carefully weighs the themes and their overlapping spatial, architectural, aesthetic, and contextual variables against a spectrum. Positioned as mediating the psychology of decision-making and the dynamics of housing in the market, the paper controls demographic variability by selecting a single context. In this study, 183 Egyptian participants act as a microcosm of the global phenomenon. The framework is proven to be statistically significant, and the findings are multidimensional, revealing nuanced differences of complex residential aesthetic preferences. At the boundary between modernized fairy-tale home aspirations and limited housing practicality, this framework holds the key to making dream homes come true by informing existing and future housing decisions.

–

Khalil, M. H. (2024). Four-walled or fourfold? Assessing if the gated community is an antidote to cities or a macrocosm of deprived houses. Cities & Health, 1-9.

This cross-sectional study evaluates the effectiveness of established and emerging city typologies, comparing whether the gated city functions as a four-walled microcosm of the deprived concrete house or serves as an antidote to urban sprawl. The fourfold model is grounded in evidence-based theories on residential greenness and urban health, resulting in four variables: greenness, sky views, social enrichment, and personal boundaries. Against the backdrop of the Greater Cairo Region, where urban evolution unfolded over two decades, leading to the emergence of gated cities, adult participants completed surveys representing pre- and post-decades. This shift in the residential landscape towards independent and gated communities allows for an assessment of well-being across city/community types and house typologies, comparing the efficacy of gated cities in relation to macro and micro typologies with the four variables. The results reveal intriguing patterns and pitfalls of gated communities, contributing to the ongoing discourse on creating inclusive and fulfilling residential environments. The study underscores the importance of examining interactive experiences within the macro-scale environment and calls for future research to extend beyond the blueprint, engaging residents with the four variables through urban and architectural designs, rather than closing doors and expecting an experience that enhances their well-being.