On November 13, 2017 Bill Gates published a post Why I’m Digging Deep Into Alzheimer’s. We at Humanness Learning had nothing to do with Alzheimer’s but we came across some interesting data about it in our research for the game to develop humanness in people and machines. We believe it’s important to share our findings. I tag this post Artificial Intelligence because understanding of the way how hippocampus works is crucial for the progress in machine learning.

Hippocampal Shrinkage: at the Core of Alzheimer’s Disease

The link between severe shrinkage of hippocampus and Alzheimer’s disease is well documented. The rate of the hippocampal atrophy correlates with the progression of the disease. Hippocampal shape and volume analysis is used to predict dementia and Alzheimer’s disease. Machine learning algorithms are applied for temporal prediction of Alzheimer’s disease progression using hippocampal surface morphometry.

Spatial Navigation Makes Hippocampus Grow

On the other side, research on the influence of video games on the human brain is accumulating evidence that people who use spatial navigation strategies while playing can increase the amount of grey matter in their hippocampus.

“Our present findings are consistent with the literature reporting that in healthy older adults there is a positive correlation between spatial memory and gray matter in the hippocampus.” researcher from McGill University in Canada concluded in their paper (2013), “With whole brain analysis, we observed that individuals with more gray matter in the hippocampus had more gray matter in anatomically and functionally connected cortical areas, namely the contralateral hippocampus, the right orbitofrontal cortex, bilateral amygdala, and bilateral parahippocampal cortex. Future studies will be needed to examine whether an intervention method focusing on spatial memory training can increase gray matter in the hippocampus and anatomically connected areas. Promoting the use of spatial strategies can be a potential avenue for intervention methods against hippocampal atrophy (Fotuhi et al., 2012).”

Researchers from the University of Montreal also confirmed in their study (2015) that, “it has been shown that young adults who navigated using a spatial strategy showed greater fMRI activity and grey matter in the hippocampus.”

The same group of scientists in their most recent work (2017) also confirmed that performing spatial navigation tasks leads to the increase of gray matter volume in hippocampus.”

To Shrink or to Grow: Spontaneous Choice

They also confirmed previous findings that people playing first person view shooter games spontaneously choose one of two different and competing navigation strategies: spatial navigation or response learning based navigation. Depending on the selected strategy and the genre of the game research participants demonstrated opposite outcomes, “Ninety hours of playing action games led to hippocampal atrophy in response learners, while 90 hours of playing 3D games led to increased grey matter within the hippocampal memory system of all participants.”

Researchers from Germany arrived in their work (2013) to similar conclusions, “An exploratory analysis showed that the entorhinal gray matter volume can be predicted by the video game genres played, such as logic/puzzle games and platform games contributing positively, and action-based role-playing games contributing negatively. Furthermore, joystick years were positively correlated with hippocampal volume.”

They confirmed their result in another study (2013), “Comparing a control with a video gaming training group that was trained for 2 months for at least 30 min per day with a platformer game, we found significant gray matter increase in right hippocampal formation, right dorsolateral prefrontal cortex and bilateral cerebellum in the training group. The hippocampus increase correlated with changes from egocentric to allocentric navigation strategy.”

The McGill University researchers in their paper cited above also established a link between the volume of hippocampal gray matter and the choice of navigation strategy by participants, “Furthermore, our results showed that those who have lower hippocampal gray matter are actually using another form of navigational strategy, the response strategy.”

Patients with preclinical Alzheimer’s disease also demonstrate reliance on response learning strategy in their real life situations. As researchers from the Washington University in St. Louis put it in their paper (2016), “Preclinical Alzheimer disease was associated with deficits in the use of a wayfinding strategy, but not a route learning strategy.”

Véronique D. Bohbot et al. from the McGill University in their paper (2007) directly referred to the potential benefit of spatial navigation strategy in fighting the Alzheimer’s disease, “Results showed that spatial learners had significantly more gray matter in the hippocampus and less gray matter in the caudate nucleus compared with response learners. Furthermore, the gray matter in the hippocampus was negatively correlated to the gray matter in the caudate nucleus, suggesting a competitive interaction between these two brain areas. In a second analysis, the gray matter of regions known to be anatomically connected to the hippocampus, such as the amygdala, parahippocampal, perirhinal, entorhinal and orbitofrontal cortices were shown to covary with gray matter in the hippocampus. Because low gray matter in the hippocampus is a risk factor for Alzheimer’s disease, these results have important implications for intervention programs that aim at functional recovery in these brain areas.”

Stories Engage Hippocampus in Dual Coding

Although spatial navigation in video games demonstrate significant results in growing the volume of hippocampus there are more complex activities performed by hippocampus which may have even greater effect on it growing and retaining its volume. Researchers from Radboud University in Netherlands underline in their paper an important complex role of hippocampal processing of stories in their paper (2016), “We show that the hippocampus, a part of the brain critically involved in representation of spatial and temporal contexts in episodic memory, also represents these storylines as separate narrative contexts.”

They wrote, “we reveal two distinct types of hippocampal representations. We showed that the hippocampus codes for nodal representations (Eichenbaum et al., 1999) where activity patterns represent the “essence” of an item in memory, which is common across different events featuring that item. We also showed that, in addition to item-specific nodal representations within a narrative, the hippocampus also codes for the entire narrative, which may reflect networks of events related through the nodal representations, which feature with relatively different frequencies in each of the two narratives. In combination, the evidence of both item-specific and narrative-specific representations in the human hippocampus suggests that human episodic memories may be subject to hierarchical organization.”

From Expected Certainty to Unexpected Uncertainty

A group of researchers from the University College London in their research paper (2013) described the distinctive reaction of different parts of hippocampus to conditions with varied levels of predictability, “We found that anterior hippocampal theta was significantly higher for the unexpected than the predictable condition. Posterior hippocampal theta, on the other hand, was higher for the unexpected when compared to the ‘expected uncertainty’ condition.”

Unexpected Uncertainty Drives Neurogenesis?

Continual production of new neurons in the hippocampus of an adult brain was first reported by Josef Altman and Goplas D. Das in 1965. Since then the process of new neurons origination from self-renewing and multipotent adult neural stem cells residing in hippocampus was well documented.

A link between this process and Alzheimer’s has been also discussed. “From a functional point of view, hippocampal neurogenesis plays an important role in structural plasticity and network maintenance.” Researchers Yangling Mu and Fred Gage from the Laboratory of Genetics of the Salk Institute for Biological Studies wrote in their research paper (2011), “Therefore, dysfunctional neurogenesis resulting from early subtle disease manifestations may in turn exacerbate neuronal vulnerability to AD (Alzheimer’s disease) and contribute to memory impairment, whereas enhanced neurogenesis may be a compensatory response and represent an endogenous brain repair mechanism.” Yangling Mu et al. pointed out that, “during maturation, newly formed DGCs (hippocampal neurons) differ substantially from their older, neighboring counterparts in terms of electrophysiological properties. Typically, they exhibit enhanced synaptic plasticity with both increased amplitude and decreased induction threshold for LTP [21, 22, 23, 24]. While the precise functional implications of the continuous production of new neurons with hyperexcitability and enhanced synaptic plasticity are still under intense investigation, it has become increasingly apparent that neurogenesis in the adult DG contributes to various types of hippocampus-dependent learning and memory.”

A group of researchers led by Yuan-Shih Hu from the University of Illinois in their paper (2009) suggested that “Complex environment experience rescues impaired neurogenesis, enhances synaptic plasticity, and attenuates neuropathology in familial Alzheimer’s disease-linked APPswe/PS1ΔE9 mice.”

Orly Lazarov et al. in their paper (2005) reported, “Cerebral deposition of β-amyloid (Aβ) peptides is an invariant pathological hallmark in brains of patients with Alzheimer’s disease (AD) and transgenic mice coexpressing familial AD-linked APP and PS1 variants. We now report that exposure of transgenic mice to an “enriched environment” results in pronounced reductions in cerebral Aβ levels and amyloid deposits, compared to animals raised under “standard housing” conditions.”

Fairy Tales: Reload

For thousands of years humans use narratives, which represent ‘enriched environment’ — a tight mix of events and actions of heroes, which probability varies from expected certainty to unexpected uncertainty in an entirely chaotic way. Both, probability of events and credibility of their cues are fluctuating in magic fairy tales unlike in any other narrative. Originally they were told to domesticate uncertainty in a sense that uncertainty should be accepted and dealt with, not avoided. Humans — the major source of uncertainty for other humans were also domesticated this way. Now we are living much longer lives than our ancestors in a much more civilised hence predictable environment. Maybe, Alzheimer’s disease it the price many of us are paying for being over domesticated. Our brain was created to tackle with any level of uncertainty including entirely unexpected unpredictable events. Maybe, it’s time to find a new way of retelling the old good fairy tales to help people who lost this ability to recover?