Zone Preference in the Visual Water Maze
June 26, 2025
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Biomedical research has evolved over the past few decades and, together with genetics, comprises one of the most investigated healthcare fields in the world. Biomedical advancement is not possible without research and development (R&D), which in turn, thrives upon funding, grants, and subsidy. A number of government, private and global organizations are philanthropic in nature and constantly funding healthcare R&D throughout the world. All it takes is the right cause to be identified by the funding organizations so that it can be pursued for the great benefit of humankind.
There are many organizations worldwide that are actively supporting researchers and medical experts to help pursue and fund their research. Funding medical research, however, is not a new phenomenon; these organizations have been around for many years. The practice finds its traces in the past century. One of the oldest and the most eminent health funding organizations is the National Institutes of Health (NIH) – founded in 1887 in New York City, USA.
Let us discuss the top 10 health funding organizations to know more about the status, accomplishments, and expenditure.
The NIH, by far, is the biggest health funding organization in the U.S and the world. It spends millions to ensure uninterrupted research and development of novel medical technology, and diagnostic modalities to improve lives.
In 2013, the NIH spent $26,081.3 million on healthcare research – the highest for any institute.
The NIH has roots in history; it has been around for more than 100 years. Healthcare owes its success to the organization per se. One of the specific reasons why NIH makes it on the top and possibly the most sought funding organization in the U.S. is due to its funding model. The NIH extensively covers research in all fields of health, and most of its research is extramural. Strictly speaking, the funding model follows a somewhat untargeted approach and, therefore, doesn’t strictly prioritize a specific area of research.
The European Commission (EC) stands second in the top 10 health funding organizations. The EC itself is not limited to health funding organizations, in fact, its two sub-programs are involved with health-related research: FP7 – Cooperation program – Health theme/Health Directorate and European Research Council (ERC).
These two sub-programs fall under the public category, and in 2013, the total expenditure of the EC was $3717.7 million, out of which $1181.7 was spend by FP7 and $783.4 by ERC. Both sub-programs are extramural, but the difference emerges in the model of funding employed by each subprogram. FP7 calls for targeted funding and allows only prioritized fields of health-related research. On the contrary, the ERC follows an untargeted approach.
The UK Medical Research Council (MRC) is one of the oldest health funding organizations after the NIH and the third-largest funding organization. In 2017/18, the MRC dedicated approximately £814.1 million for biomedical research.
As far as the targeted researchers go, the MRC welcomes both intramural and extramural research work, therefore, encouraging the medical professionals not only from the UK but across the globe. As far as the funding model of MRC is concerned, it follows a mixed approach, i.e., it allows both untargeted and targeted areas, allowing broad areas of the medical field to be placed under untargeted areas.
The Inserm, a French medical research public funding institute, falls fourth on the list. In 2013, the total expenditure of Inserm in the field of research amounted to $1042.1 million. The Inserm, though European, upholds different standards with respect to other European funding institutes in terms of granting the funds, i.e., it is purely intramural.
The United States Department of Defense (US DoD) addresses health funding via the Congressionally Directed Medical Research Program (CDMRP), which is a public funding organization. Though the US DoD organizes 14 research programs, the only available figures of the expenditure are provided of CDMRP.
According to the 2012 statistics, $409.0 million were spent by CDMRP in pursuing health-related research, whereas the total expenditure of the US DoD was $1017.7 million. Since the CDMRP expenses have been publically declared, it must be mentioned that CDMRP is largely extramural and rarely accepts intramural opportunities. The funding mechanism includes untargeted but prioritized research topics, as well as targeted research on a small scale.
The Wellcome Trust is a philanthropic organization situated in the Great Britain Republic. According to the 2013 statistics, the Wellcome Trust managed to spend $909.1 million on health-related research. As per statistics, the Wellcome Trust mainly invests in extramural research though it does not exclude intramural research. Furthermore, the funding mechanism of the Wellcome Trust is designed to encourage the untargeted approach, but it also welcomes small-scale targeted research.
The CIHR is a public funding organization based in Canada and stands 7th in the list of top 10 health funding organization. Reports from 2012 reveal that CIHR’s total expenditure in health research $883.6 million. The CIHR involves purely extramural research, and according to the data provided, the CIHR focuses on both targeted and untargeted research, but prefers and highly prioritizes untargeted research while selectively choosing targeted research.
NHMRC is public health funding organizations based in Australia. In 2013, the total expenditure of NHMRC was $777.6 million. Like most of the organizations present in the list, the NHMRC too relies on extramural researchers and prioritizes mainly untargeted research, albeit it keeps some space for targeted research on a small scale as well.
The Howard Hughes Medical Institute is one of the many funding organizations of the U.S. It is basically a philanthropic organization. In 2013, this organization spent $752.0 million on health research.
As far as the distribution mechanism goes, it must be mentioned here that the HHMI is extramural, but it funds intramural research as well. All of the researchers represent various universities and research institutes, with the exception of the Janelia Research Campus (one of the HHMI’s institutes). Furthermore, the funding mechanism of the HHMI is strictly untargeted and does not mention any priorities related to targeted research.
The GFR, a German research foundation, is another European health funding institute. Statistics from 2012 reveal that the GFR managed to spend $630.6 million on health research.
Its distribution mechanism further reveals that the GFR is only extramural. However, as far as its funding mechanism goes, it relies on a mixed approach. It prefers both untargeted and targeted research but prioritizes untargeted research and focuses itself on funding smaller targeted research.
While the aforementioned institutes were ranked on the basis of their expenditure, it is also important to mention other notable institutes and organizations that help fund biomedical and health research. The Official Development Agencies (ODA) have played a significant role in empowering research development all over the world. Though the expenditures of ODA agencies are not as much as that of the aforementioned organizations, they are sought by medical professionals all around the world to help fund their research.
As far as the ODA agencies go, the top three funding organizations include the United States Agency for International Development (USAID) with the total expenditure of $184.4 million in 2012; the UK Department for International Development (DFID) covering $97.5 million in 2014; and Grand Challenges Canada $46.3 million in 2013.
Multilateral organizations can be found in health research. It must be mentioned here that like the ODA, multilateral organizations are not limited to health funding only. For instance, the USAID offers programs that cover not just health-related research and projects but also focus on education, gender equality, women empowerment, energy, etc. Multilateral organizations, on the other hand, may or may not always grant funds on health research, but some do tend to focus their funding on health projects and research. Funding for a health-based project holds different criteria and benchmarks.
Multilateral organizations that help fund health research include the World Health Organization (WHO) which, according to the available statistics from 2006, spent $135.0 million.
The World Bank in 2011 funded $2.1 million for health-related research. There are also other organizations such as the UNAIDS, UNITAIDS, as well as, Global Fund to Fight AIDS, Tuberculosis, and Malaria, but due to the unavailability of the data, their expenditure cannot be shared. Needless to say, these organizations play a vital role in funding health research all around the world and also fund projects that help improve the living standard of people with poor health conditions.
In conclusion, every health funding organization values different standards. Regardless of intramural or extramural research; research priorities; or the fact that how much expenditure is spent by organizations, it all comes down to the field of research for which the funding is being applied. Every organization prioritizes its own field of health research which can be as diverse as one can imagine, which is why applying for funds in these organizations requires high merit and considerable dedication from the researcher’s end.
In behavioral neuroscience, the Open Field Test (OFT) remains one of the most widely used assays to evaluate rodent models of affect, cognition, and motivation. It provides a non-invasive framework for examining how animals respond to novelty, stress, and pharmacological or environmental manipulations. Among the test’s core metrics, the percentage of time spent in the center zone offers a uniquely normalized and sensitive measure of an animal’s emotional reactivity and willingness to engage with a potentially risky environment.
This metric is calculated as the proportion of time spent in the central area of the arena—typically the inner 25%—relative to the entire session duration. By normalizing this value, researchers gain a behaviorally informative variable that is resilient to fluctuations in session length or overall movement levels. This makes it especially valuable in comparative analyses, longitudinal monitoring, and cross-model validation.
Unlike raw center duration, which can be affected by trial design inconsistencies, the percentage-based measure enables clearer comparisons across animals, treatments, and conditions. It plays a key role in identifying trait anxiety, avoidance behavior, risk-taking tendencies, and environmental adaptation, making it indispensable in both basic and translational research contexts.
Whereas simple center duration provides absolute time, the percentage-based metric introduces greater interpretability and reproducibility, especially when comparing different animal models, treatment conditions, or experimental setups. It is particularly effective for quantifying avoidance behaviors, risk assessment strategies, and trait anxiety profiles in both acute and longitudinal designs.
This metric reflects the relative amount of time an animal chooses to spend in the open, exposed portion of the arena—typically defined as the inner 25% of a square or circular enclosure. Because rodents innately prefer the periphery (thigmotaxis), time in the center is inversely associated with anxiety-like behavior. As such, this percentage is considered a sensitive, normalized index of:
Critically, because this metric is normalized by session duration, it accommodates variability in activity levels or testing conditions. This makes it especially suitable for comparing across individuals, treatment groups, or timepoints in longitudinal studies.
A high percentage of center time indicates reduced anxiety, increased novelty-seeking, or pharmacological modulation (e.g., anxiolysis). Conversely, a low percentage suggests emotional inhibition, behavioral avoidance, or contextual hypervigilance. reduced anxiety, increased novelty-seeking, or pharmacological modulation (e.g., anxiolysis). Conversely, a low percentage suggests emotional inhibition, behavioral avoidance, or contextual hypervigilance.
The percentage of center time is one of the most direct, unconditioned readouts of anxiety-like behavior in rodents. It is frequently reduced in models of PTSD, chronic stress, or early-life adversity, where animals exhibit persistent avoidance of the center due to heightened emotional reactivity. This metric can also distinguish between acute anxiety responses and enduring trait anxiety, especially in longitudinal or developmental studies. Its normalized nature makes it ideal for comparing across cohorts with variable locomotor profiles, helping researchers detect true affective changes rather than activity-based confounds.
Rodents that spend more time in the center zone typically exhibit broader and more flexible exploration strategies. This behavior reflects not only reduced anxiety but also cognitive engagement and environmental curiosity. High center percentage is associated with robust spatial learning, attentional scanning, and memory encoding functions, supported by coordinated activation in the prefrontal cortex, hippocampus, and basal forebrain. In contrast, reduced center engagement may signal spatial rigidity, attentional narrowing, or cognitive withdrawal, particularly in models of neurodegeneration or aging.
The open field test remains one of the most widely accepted platforms for testing anxiolytic and psychotropic drugs. The percentage of center time reliably increases following administration of anxiolytic agents such as benzodiazepines, SSRIs, and GABA-A receptor agonists. This metric serves as a sensitive and reproducible endpoint in preclinical dose-finding studies, mechanistic pharmacology, and compound screening pipelines. It also aids in differentiating true anxiolytic effects from sedation or motor suppression by integrating with other behavioral parameters like distance traveled and entry count (Prut & Belzung, 2003).
Sex-based differences in emotional regulation often manifest in open field behavior, with female rodents generally exhibiting higher variability in center zone metrics due to hormonal cycling. For example, estrogen has been shown to facilitate exploratory behavior and increase center occupancy, while progesterone and stress-induced corticosterone often reduce it. Studies involving gonadectomy, hormone replacement, or sex-specific genetic knockouts use this metric to quantify the impact of endocrine factors on anxiety and exploratory behavior. As such, it remains a vital tool for dissecting sex-dependent neurobehavioral dynamics.
The percentage of center time is one of the most direct, unconditioned readouts of anxiety-like behavior in rodents. It is frequently reduced in models of PTSD, chronic stress, or early-life adversity. Because it is normalized, this metric is especially helpful for distinguishing between genuine avoidance and low general activity.
Environmental Control: Uniformity in environmental conditions is essential. Lighting should be evenly diffused to avoid shadow bias, and noise should be minimized to prevent stress-induced variability. The arena must be cleaned between trials using odor-neutral solutions to eliminate scent trails or pheromone cues that may affect zone preference. Any variation in these conditions can introduce systematic bias in center zone behavior. Use consistent definitions of the center zone (commonly 25% of total area) to allow valid comparisons. Software-based segmentation enhances spatial precision.
Evaluating how center time evolves across the duration of a session—divided into early, middle, and late thirds—provides insight into behavioral transitions and adaptive responses. Animals may begin by avoiding the center, only to gradually increase center time as they habituate to the environment. Conversely, persistently low center time across the session can signal prolonged anxiety, fear generalization, or a trait-like avoidance phenotype.
To validate the significance of center time percentage, it should be examined alongside results from other anxiety-related tests such as the Elevated Plus Maze, Light-Dark Box, or Novelty Suppressed Feeding. Concordance across paradigms supports the reliability of center time as a trait marker, while discordance may indicate task-specific reactivity or behavioral dissociation.
When paired with high-resolution scoring of behavioral events such as rearing, grooming, defecation, or immobility, center time offers a richer view of the animal’s internal state. For example, an animal that spends substantial time in the center while grooming may be coping with mild stress, while another that remains immobile in the periphery may be experiencing more severe anxiety. Microstructure analysis aids in decoding the complexity behind spatial behavior.
Animals naturally vary in their exploratory style. By analyzing percentage of center time across subjects, researchers can identify behavioral subgroups—such as consistently bold individuals who frequently explore the center versus cautious animals that remain along the periphery. These classifications can be used to examine predictors of drug response, resilience to stress, or vulnerability to neuropsychiatric disorders.
In studies with large cohorts or multiple behavioral variables, machine learning techniques such as hierarchical clustering or principal component analysis can incorporate center time percentage to discover novel phenotypic groupings. These data-driven approaches help uncover latent dimensions of behavior that may not be visible through univariate analyses alone.
Total locomotion helps contextualize center time. Low percentage values in animals with minimal movement may reflect sedation or fatigue, while similar values in high-mobility subjects suggest deliberate avoidance. This metric helps distinguish emotional versus motor causes of low center engagement.
This measure indicates how often the animal initiates exploration of the center zone. When combined with percentage of time, it differentiates between frequent but brief visits (indicative of anxiety or impulsivity) versus fewer but sustained center engagements (suggesting comfort and behavioral confidence).
The delay before the first center entry reflects initial threat appraisal. Longer latencies may be associated with heightened fear or low motivation, while shorter latencies are typically linked to exploratory drive or low anxiety.
Time spent hugging the walls offers a spatial counterbalance to center metrics. High thigmotaxis and low center time jointly support an interpretation of strong avoidance behavior. This inverse relationship helps triangulate affective and motivational states.
By expressing center zone activity as a proportion of total trial time, researchers gain a metric that is resistant to session variability and more readily comparable across time, treatment, and model conditions. This normalized measure enhances reproducibility and statistical power, particularly in multi-cohort or cross-laboratory designs.
For experimental designs aimed at assessing anxiety, exploratory strategy, or affective state, the percentage of time spent in the center offers one of the most robust and interpretable measures available in the Open Field Test.
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