How physical exercise and fitness improves your brain function
Neurogenesis — the creation of new brain cells — occurs of course at a great rate in the very young. For a long time, it was not thought to occur in adult brains — once you were grown, it was thought, all you could do was watch your brain cells die!
Adult neurogenesis (the creation of new brain cells in adult brains) was first discovered in 1965, but only recently has it been accepted as a general phenomenon that occurs in many species, including humans (1998).
It's now widely accepted that adult neurogenesis occurs in the subgranular zone of the dentate gyrus within the hippocampus and the subventricular zone (SVZ) lining the walls of the lateral ventricles within the forebrain. It occurs, indeed, at a quite frantic rate — some 9000 new cells are born in the dentate gyrus every day in young adult rat brains — but under normal circumstances, at least half of those new cells will die within one or two months.
The neurons produced in the SVZ are sent to the olfactory bulb, while those produced in the dentate gyrus are intended for the hippocampus.
Adult neurogenesis might occur in other regions, but this is not yet well-established. However, recent research has found that small, non-pyramidal, inhibitory interneurons are being created in the cortex and striatum. These new interneurons appear to arise from a previously unknown class of local precursor cells. These interneurons make and secrete GABA (see below for why GABA is important), and are thought to play a role in regulating larger types of neurons that make long-distance connections between brain regions.
New neurons are spawned from the division of neural precursor cells — cells that have the potential to become neurons or support cells. How do they decide whether to remain a stem cell, turn into a neuron, or a support cell (an astrocyte or oligodendrocyte)?
Observation that neuroblasts traveled to the olfactory bulb from the SVZ through tubes formed by astrocytes has led to an interest in the role of those support cells. It's now been found that astrocytes encourage both precursor cell proliferation and their maturation into neurons — precursor cells grown on glia divide about twice as fast as they do when grown on fibroblasts, and are about six times more likely to become neurons.
Adult astrocytes are only about half as effective as embryonic astrocytes in promoting neurogenesis.
It’s been suggested that the role of astrocytes may help explain why neurogenesis only occurs in certain parts of the brain — it may be that there’s something missing from the glial cells in those regions.
The latest research suggests that the astrocytes influence the decision through a protein that it secretes called Wnt3. When Wnt3 proteins were blocked in the brains of adult mice, neurogenesis decreased dramatically; when additional Wnt3 was introduced, neurogenesis increased.
How are these new neurons then integrated into existing networks? Mouse experiments have found that the brain chemical called GABA is critical. Normally, GABA inhibits neuronal signals, but it turns out that with new neurons, GABA has a different effect: it excites them, and prepares them for integration into the adult brain. Thus a constant flood of GABA is needed initially; the flood then shifts to a more targeted pulse that gives the new neuron specific connections that communicate using GABA; finally, the neuron receives connections that communicate via another chemical, glutamate. The neuron is now ready to function as an adult neuron, and will respond to glutamate and GABA as it should.
The creation and development of new neurons in the adult brain is very much a "hot" topic right now — it's still very much a work-in-progress. However, it is clear that other brain chemicals are also involved. An important one is BDNF (brain-derived neurotrophic factor), which seems to be needed during the proliferation of hippocampal precursor cells to trigger their transformation into neurons.
Other growth factors have been found to stimulate proliferation of hippocampal progenitor cells: FGF-2 (fibroblast growth factor-2) and EGF (epidermal growth factor).
Recently it has been discovered that the normal form of the prion protein which, when malformed, causes mad cow disease, is also involved in neurogenesis. These proteins, in their normal form, are found throughout our bodies, and particularly in our brains. Now it seems that the more of these prion proteins that are available, the faster neural precursor cells turn into neurons.
The immune system's T cells (which recognize brain proteins) are also critically involved in enabling neurogenesis to occur. Among mice given environmental enrichment, only those with healthy T-cells had their production of new neurons boosted.
A number of factors have been found to affect the creation and survival of new neurons. For a start, damage to the brain (from a variety of causes) can provoke neurogenesis.
Moderate alcohol consumption over a relatively long period of time can also enhance the formation of new nerve cells in the adult brain (this may be related to alcohol's enhancement of GABA's function). Excess alcohol, however, has a detrimental effect on the formation of new neurons in the adult hippocampus. But although neurogenesis is inhibited during alcohol dependency, it does recover. A pronounced increase in new neuron formation in the hippocampus was found within four-to-five weeks of abstinence. This included a twofold burst in brain cell proliferation at day seven of abstinence.
Most drugs of abuse such as nicotine, heroine, and cocaine suppress neurogenesis, but a new study suggests that cannabinoids also promote neurogenesis. The study involved a synthetic cannabinoid, which increased the proliferation of progenitor cells in the hippocampal dentate gyrus of mice, in a similar manner as some antidepressants have been shown to do. The cannabinoid also produced similar antidepressant effects. Further research is needed to confirm this early finding.
If antidepressants promote neurogenesis, it won't be surprising to find that chronic stress, anxiety and depression are associated with losing hippocampal neurons. A rat study has also found that stress in early life can permanently impair neurogenesis in the hippocampus.
Showing the other side of this picture, perhaps, an intriguing rat study found that status affected neurogenesis in the hippocampus, with high-status animals having around 30% more neurons in their hippocampus after being placed in a naturalistic setting with other rats.
Also, a study into the brains of songbirds found that birds living in large groups have more new neurons and probably a better memory than those living alone.
Both physical activity and environmental enrichment (“mental stimulation”) have been shown to affect both how many cells are born in the dentate gyrus of rats and how many survive. Learning that uses the hippocampus has also been shown to have a positive effect, although results here have been inconsistent.
Inconsistent results from studies looking at neurogenesis are, it is suggested, largely because of a confusion between proliferation and survival. Neurogenesis is measured in terms of these two factors, which researchers often fail to distinguish between: the generation of new brain cells, and their survival. But these are separate factors, that are independently affected by various factors.
The inconsistency found in the effects of learning may also be partly explained by the complex nature of the effects. For example, during the later phase of learning, when performance is starting to plateau, neurons created during the late phase were more likely to survive, but neurons created during the early phase of more rapid learning disappeared. It’s speculated that that this may be a “pruning” process by which cells that haven’t made synaptic connections are removed from the network.
And finally, rodent studies suggest a calorie-restricted diet may also be of benefit.
A few years ago, we were surprised by news that new neurons could be created in the adult brain. However, it’s remained a tenet that adult neurons don’t grow — this because researchers have found no sign that any structural remodelling takes place in an adult brain. Now a mouse study using new techniques has revealed that dramatic restructuring occurs in the less-known, less-accessible inhibitory interneurons. Dendrites (the branched projections of a nerve cell that conducts electrical stimulation to the cell body) show sometimes dramatic growth, and this growth is tied to use, supporting the idea that the more we use our minds, the better they will be.
For more, see the research reports
Following rat studies, a study involving 36 healthy young adults has found that 10 minutes of light exercise (such as tai chi, yoga, or walking) significantly improved highly detailed memory processing and resulted in increased activity in the hippocampus.
It also boosted connectivity between the hippocampus and cortical regions that support detailed memory processing (parahippocampal, angular, and fusiform gyri), and the degree of improvement in this connectivity predicted the extent of this memory improvement for an individual.
The memory task involved remembering details of pictures of objects from everyday life, some of which were very similar to other pictures, requiring participants to distinguish between the different memories.
Mood change was also assessed, and the researchers ruled out this as a cause of the improved memory.
Another recent study found that 15 minutes of cardiovascular exercise after learning a new motor skill resulted in better skill learning when tested a day later.
Exercise was also found to decrease desynchronization in beta brainwaves and increase their connectivity between hemispheres. The degree of improvement in skill learning reflected changes in beta-wave desynchronization. It appears that exercise helped the brain become more efficient in performing the skill.
The motor skill consisted of gripping an object akin to a gamers' joystick and using varying degrees of force to move a cursor up and down to connect red rectangles on a computer screen as quickly as possible.
Note that there was no difference between the two groups (those who exercised and those who didn’t) 8 hours after learning — the difference didn’t appear until after participants had slept. Sleep helps consolidate skill learning.
Suwabe, K. 2018. Rapid stimulation of human dentate gyrus function with acute mild exercise. Proceedings of the National Academy of Sciences Oct 2018, 115 (41) 10487-10492; DOI: 10.1073/pnas.1805668115
 Dal Maso, F., Desormeau B., Boudrias M-H., & Roig M.
(2018). Acute cardiovascular exercise promotes functional changes in cortico-motor networks during the early stages of motor memory consolidation.
NeuroImage. 174, 380 - 392.
A randomized clinical trial involving 103 teenage athletes who sustained concussions while playing sports found that those who underwent a supervised, aerobic exercise program took significantly less time to recover compared to those who instead engaged in mild stretching.
Those in the exercise program took on average 13 days to recover, while those in the control group, who performed placebo-like stretching exercises (that would not substantially elevate heart rate), took 17 days. In addition, only two patients in the exercise program took longer than four weeks to recover, compared to seven patients in the control group.
The treatment began within the first week of a concussion in adolescents, after a few days of rest. Each exercise program was individually tailored, on the basis of their performance on the Buffalo Concussion Treadmill Test, and each participant was given a heart rate monitor to ensure they didn’t exceed the given threshold. The assigned exercise took about 20 minutes each day.
The exercise “dose” was evaluated weekly, and increased as the patient’s condition improved.
Patients were also told to avoid contact sports, gym class, or team practice, and excessive use of electronic devices, since that can also aggravate symptoms.
Adolescents typically take the longest to recover from concussion.
The findings directly contradict the conventional approach to concussion, which often consists of nearly total rest, eliminating most physical and mental activities, including schoolwork.
 Leddy, J. J., Haider M. N., Ellis M. J., Mannix R., Darling S. R., Freitas M. S., et al.
(2019). Early Subthreshold Aerobic Exercise for Sport-Related Concussion: A Randomized Clinical Trial.
A small study has found that a 12-week exercise program significantly improved cognition in both older adults with MCI and those who were cognitively healthy, but that effect on blood flow in the brain was different in these two groups.
While the exercise increased cerebral blood flow in the frontal cortex of those in the healthy group, those with MCI experienced decreases in cerebral blood flow. It has been speculated that the brain responds to early difficulties by increasing cerebral blood flow. This suggests that exercise may have the potential to reduce this compensatory blood flow and improve cognitive efficiency in those who are in the very early stages of Alzheimer's Disease.
The exercise training program consisted of four 30-minute sessions of moderate-intensity treadmill walking per week.
Both working memory and verbal fluency were tested (using the Rey Auditory Verbal Learning Test, and the Controlled Oral Word Association Test).
Changes in cerebral blood flow were measured in specific brain regions that are known to be involved in the pathogenesis of Alzheimer's disease, including the insula, the anterior cingulate cortex, and the inferior frontal gyrus.
Among those with MCI, decreased blood flow in the left insula and anterior cingulate cortex was strongly associated with improved verbal fluency.
Alfini, A. J. et al. 2019. Resting Cerebral Blood Flow After Exercise Training in Mild Cognitive Impairment. Journal of Alzheimer's Disease, 67 (2), 671-684.
A number of studies have found that physical exercise can help delay the onset of dementia, however the ability of exercise to slow the decline once dementia has set in is a more equivocal question. A large new study answers this question in the negative.
The study involved 494 people with mild-to-moderate dementia (average age 77; 61% male), of whom 329 were randomly assigned to a four-month aerobic and strength exercise programme and 165 were assigned to usual care. The exercise program was personalized, and involved two 60-90 minute gym sessions every week, plus a further hour at home. Nearly two-thirds of the exercise group attended more than three-quarters of the gym sessions.
While the exercise group did get physically fitter, their cognitive fitness (as measured by ADAS-cog score) actually worsened slightly.
The researchers emphasize that this was a specialized and intense exercise program, and in no way should it be taken to mean that gentle exercise, which is good for dementia sufferers, should be avoided.
 Lamb, S. E., Sheehan B., Atherton N., Nichols V., Collins H., Mistry D., et al.
(2018). Dementia And Physical Activity (DAPA) trial of moderate to high intensity exercise training for people with dementia: randomised controlled trial.
BMJ. 361, k1675.
A Spanish study involving 101 overweight/obese children (aged 8-11) has found that aerobic capacity and motor ability is associated with a greater volume of gray matter in several cortical and subcortical brain regions.
Aerobic capacity was associated with greater gray matter volume in the premotor cortex, supplementary motor cortex, hippocampus, caudate nucleus, inferior temporal gyrus, parahippocampal gyrus, and the calcarine cortex. Three of these regions (premotor cortex, supplementary motor cortex and hippocampus) were also related to better academic performance.
Motor ability (speed and agility) was associated with a greater gray matter volume in two regions essential for language processing and reading: the inferior frontal gyrus and the superior temporal gyrus. Both of these were also associated with better academic performance.
Muscular strength showed no independent association with gray matter volume in any brain region.
The researchers suggest that increases in cardiorespiratory fitness and “speed-agility” may counteract the known harmful effect of obesity on brain structure and academic performance during childhood.
 Esteban-Cornejo, I., Cadenas-Sanchez C., Contreras-Rodriguez O., Verdejo-Roman J., Mora-Gonzalez J., Migueles J. H., et al.
(2017). A whole brain volumetric approach in overweight/obese children: Examining the association with different physical fitness components and academic performance. The ActiveBrains project.
NeuroImage. 159, 346 - 354.
A Finnish study involving over 1000 older adults suggests that a counselling program can prevent cognitive decline even among those with the Alzheimer’s gene.
The study involved 1,109 older adults (aged 60-77) of whom 362 were carriers of the APOE4 gene. Some of the participants received regular lifestyle counselling (general health advice), while the rest received “enhanced” lifestyle counselling, involving nutrition counselling, physical and cognitive exercises, and support in managing the risk of cardiovascular diseases.
Earlier findings from the FINGER (Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability) trial showed that the regular lifestyle counselling group had a significantly increased risk of cognitive and functional impairment compared to the group receiving enhanced counselling. This analysis shows that this holds true even for those with the Alzheimer's gene, and indeed, might even be more helpful for carriers of the risky gene.
The findings emphasize the importance of early prevention strategies that target multiple modifiable risk factors simultaneously.
 Solomon, A., Turunen H., Ngandu T., Peltonen M., Levälahti E., Helisalmi S., et al.
(2018). Effect of the Apolipoprotein E Genotype on Cognitive Change During a Multidomain Lifestyle Intervention: A Subgroup Analysis of a Randomized Clinical Trial.
JAMA Neurology. 75(4), 462 - 470.
A British study using data from 475,397 participants has shown that, on average, stronger people performed better across every test of brain functioning used. Tests looked at reaction speed, reasoning, visuospatial memory, prospective memory, and working memory (digit span). The relationship between muscular strength and brain function was consistently strong in both older and younger adults (those under 55 and those over), contradicting previous research showing it only in older adults.
The study also found that maximal handgrip was strongly correlated with both visuospatial memory and reaction time in 1,162 people with schizophrenia (prospective memory also approached statistical significance).
The finding raises the intriguing possibility that weight training could be particularly beneficial for people with mental health conditions, such as schizophrenia, major depression and bipolar disorder.
Full text available online at https://doi.org/10.1093/schbul/sby034
 Firth, J., Stubbs B., Vancampfort D., Firth J. A., Large M., Rosenbaum S., et al.
(Submitted). Grip Strength Is Associated With Cognitive Performance in Schizophrenia and the General Population: A UK Biobank Study of 476559 Participants.
A Finnish study involving 338 older adults (average age 66) has found that greater muscle strength is associated with better cognitive function.
Muscle strength was measured utilising handgrip strength, three lower body exercises such as leg extension, leg flexion and leg press and two upper body exercises such as chest press and seated row.
Handgrip strength, easy to measure, has been widely used as a measure of muscle strength, and has been associated with dementia risk among the very old. However, in this study, handgrip strength on its own showed no association with cognitive function. But both upper body strength and lower body strength were independently associated with cognitive function.
It may be that handgrip strength is only useful for older, more cognitively impaired adults.
These are gender-specific associations — muscle strength was significantly greater in men, but there was no difference in cognitive performance between men and women.
The finding is supported by previous research that found a link between walking speed and cognition in older adults, and by a 2015 study that found a striking correlation between leg power and cognition.
This 10-year British study involved 324 older female twins (average age 55). Both the degree of cognitive decline over the ten year period, and the amount of gray matter, was significantly correlated with high muscle fitness (measured by leg extension muscle power). The correlation was greater than for any other lifestyle factor tested
 Pentikäinen, H., Savonen K., Komulainen P., Kiviniemi V., Paajanen T., Kivipelto M., et al.
(2017). Muscle strength and cognition in ageing men and women: The DR's EXTRA study.
European Geriatric Medicine. 8(3), 275 - 277.
 Steves, C. J., Mehta M. M., Jackson S. H. D., & Spector T. D.
(2015). Kicking Back Cognitive Ageing: Leg Power Predicts Cognitive Ageing after Ten Years in Older Female Twins.
A new MRI technique has revealed that it is the structural integrity of the hippocampus more than its size that reflects fitness and correlates with cognitive performance.
Research has focused on hippocampal size because it is easier to measure, and in children and older adults there are strong correlations between hippocampal size and memory. But this is less true for healthy, young adults. This new, subtler, technique reveals that something else is going on — something that has probably been masked by the effects of size in older adults (whose hippocampi are shrinking) and younger children (whose brains are still growing).
The technique measures viscoelasticity. If the hippocampus is more elastic, memory is better. When it’s more viscous, memory is worse. Those with better aerobic fitness had better hippocampal elasticity.
 Schwarb, H., Johnson C. L., Daugherty A. M., Hillman C. H., Kramer A. F., Cohen N. J., et al.
(2017). Aerobic fitness, hippocampal viscoelasticity, and relational memory performance.
NeuroImage. 153, 179 - 188.
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