Environmental enrichment (neural)
Environmental enrichment is the stimulation of the brain by its physical and social surroundings. Brains in richer, more stimulating environments have higher rates of synaptogenesis and more complex dendrite arbors, leading to increased brain activity. This effect takes place primarily during neurodevelopment, but also during adulthood to a lesser degree. With extra synapses there is also increased synapse activity, leading to an increased size and number of glial energy-support cells. Environmental enrichment also enhances capillary vasculation, providing the neurons and glial cells with extra energy. The neuropil (neurons, glial cells, capillaries, combined together) expands, thickening the cortex. Research on rodent brains suggests that environmental enrichment may also lead to an increased rate of neurogenesis.
Research on animals finds that environmental enrichment could aid the treatment and recovery of numerous brain-related dysfunctions, including Alzheimer's disease and those connected to aging, whereas a lack of stimulation might impair cognitive development. Moreover, this research also suggests that environmental enrichment leads to a greater level of cognitive reserve, the brain's resilience to the effects of conditions such as aging and dementia.
Research on humans suggests that lack of stimulation delays and impairs cognitive development. Research also finds that attaining and engaging in higher levels of education, environments in which people participate in more challenging cognitively stimulating activities, results in greater cognitive reserve.
- 1 Early research
- 2 Synapses
- 3 Neurogenesis
- 4 Mechanisms
- 5 Rehabilitation and resilience
- 5.1 Neurological rehabilitation
- 5.2 Cognitive reserve
- 6 Humans
- 7 See also
- 8 Notes
- 9 Bibliography
- 10 External links
Donald O. Hebb in 1947 found that rats raised as pets performed better on problem solving tests than rats raised in cages. His research, however, did not investigate the brain nor use standardized impoverished and enriched environments. Research doing this first was started in 1960 at the University of California, Berkeley by Mark Rosenzweig, who compared single rats in normal cages, and those placed in ones with toys, ladders, tunnels, running wheels in groups. This found that growing up in enriched environments affected enzyme cholinesterase activity. This work led in 1962 to the discovery that environmental enrichment increased cerebral cortex volume. In 1964, it was found that this was due to increased cerebral cortex thickness and greater synapse and glial numbers.
Also starting around 1960, Harry Harlow studied the effects of maternal and social deprivation on rhesus monkey infants (a form of environmental stimulus deprivation). This established the importance of social stimulation for normal cognitive and emotional development.
Rats raised with environmental enrichment have thicker cerebral cortices(3.3–7%) that contain 25% more synapses. This effect of environmental richness upon the brain occurs whether it is experienced immediately following birth, after weaning, or during maturity. When synapse numbers increase in adults, they can remain high in number even when the adults are returned to impoverished environment for 30 days suggesting that such increases in synapse numbers are not necessarily temporary. However, the increase in synapse numbers has been observed generally to reduce with maturation. Stimulation affects not only synapses upon pyramidal neurons (the main projecting neurons in the cerebral cortex) but also stellate ones (that are usually interneurons). It also can affect neurons outside the brain in the retina.
Environmental enrichment affects the complexity and length of the dendrite arbors (upon which synapses form). Higher-order dendrite branch complexity is increased in enriched environments, as can the length, in young animals, of distal branches.
Activity and energy consumption
Synapses in animals in enriched environments show evidence of increased synapse activation. Synapses tend to also be much larger. Gamma oscillations become larger in amplitude in the hippocampus. This increased energy consumption is reflected in glial and local capillary vasculation that provides synapses with extra energy.
- Glial cell numbers per neuron increase 12–14%
- The direct apposition area of glial cells with synapses expands by 19%
- The volume of glial cell nuclei for each synapse is higher by 37.5%
- The mean volume of mitochondria per neuron is 20% greater
- The volume of glial cell nuclei for each neuron is 63% higher
- Capillary density is increased.
- Capillaries are wider (4.35 μm compared to 4.15 μm in controls)
- Shorter distance exist between any part of the neuropil and a capillary (27.6 μm compared to 34.6 μm)
These energy related changes to the neuropil are responsible for increasing the volume of the cerebral cortex (the increase in synapse numbers contributes in itself hardly any extra volume).
Motor learning stimulation
Part of the effect of environmental enrichment is providing opportunities to acquire motor skills. Research upon “acrobatic” skill learning in the rat shows that it leads to increased synapse numbers.
Environmental enrichment can also lead to the formation of neurons (at least in rats) and reverses the loss of neurons in the hippocampus and memory impairment following chronic stress. However, its relevance has been questioned for the behavioral effects of enriched environments.
Enriched environments affect the expression of genes in the cerebral cortex and the hippocampus that determine neuronal structure. At the molecular level, this occurs through increased concentrations of the neurotrophins NGF, NT-3, and changes in BDNF. This alters the activation of cholinergic neurons, 5-HT, and beta-adrenolin. Another effect is to increase proteins such as synaptophysin and PSD-95 in synapses. Changes in Wnt signaling have also been found to mimic in adult mice the effects of environmental enrichment upon synapses in the hippocampus. Increase in neurons numbers could be linked to changes in VEGF.
Rehabilitation and resilience
Research in animals suggests that environmental enrichment aids in recovery from an array of neurological disorders and cognitive impairments. There are two mains areas of focus: neurological rehabilitation and cognitive reserve, the brain's resistance to the effects of exposure to physical, natural, and social threats. Although most of these experiments used animal subjects, mainly rodents, researchers have pointed to the affected areas of animal brains to which human brains are most similar and used their findings as evidence to show that humans would have comparable reactions to enriched environments. The tests done on animals are thus meant to represent human simulations for the following list of conditions.
A study conducted in 2011 led to the conclusion that environmental enrichment vastly improves the cognitive ability of children with autism. The study found that autistic children who receive olfactory and tactile stimulation along with exercises that stimulated other paried sensory modalities clinically improved by 42 percent while autistic children not receiving this treatment clinically improved by just 7 percent. The same study also showed that there was significant clinical improvement in autistic children exposed to enriched sensorimotor environments, and a vast majority of parents reported that their child's quality of life was much better with the treatment.
Through environmental enrichment, researchers were able to enhance and partially repair memory deficits in mice between ages of 2 to 7 months with characteristics of Alzheimer's disease. Mice in enriched environments performed significantly better on object recognition tests and the Morris Water Maze than they had when they were in standard environments. It was thus concluded that environmental enrichment enhances visual and learning memory for those with Alzheimer's.
Research has indicated that environmental enrichment can help relieve motor and psychiatric deficits caused by Huntington's disease. It also improves lost protein levels for those with the disease, and prevents striatal and hippocampal deficits in the BDNF, located in the hippocampus. These findings have led researchers to suggest that environmental enrichment has a potential to be a possible form of therapy for those with Huntington's.
Multiple studies have reported that environmental enrichment for adult mice helps relieve neuronal death, which is particularly beneficial to those with Parkinson's disease. A more recent study shows that environmental enrichment particularly affects the nigrostriatal pathway, which is important for managing dopamine and acetylcholine levels, critical for motor deficits. Moreover, it was found that environmental enrichment has beneficial effects for the social implications of Parkinson's disease.
Research done in animals has shown that subjects recovering in an enriched environment 15 days after having a stroke had significantly improved neurobehavioral function. In addition these same subjects showed greater capability of learning and larger infarct post-intervention than those who were not in an enriched environment. It was thus concluded that environmental enrichment had a considerable beneficial effect on the learning and sensorimotor functions on animals post-stroke. A 2013 study also found that environmental enrichment socially benefits patients recovering from stroke. Researchers in that study concluded that stroke patients in enriched environments in assisted-care facilities are much more likely to be engaging with other patients during normal social hours instead of being alone or sleeping.
A 2008 study found that environmental enrichment was significant in aiding recovery of motor coordination and some recovery of BDNF levels in female mice with conditions similar to those of Rett syndrome. Over the course of 30 weeks female mice in enriched environments showed superior ability in motor coordination to those in standard conditions. Although they were unable to have full motor capability, they were able to prevent a more severe motor deficit by living in an enriched environment. These results combined with increased levels of BDNF in the cerebellum led researchers to conclude that an enriched environment that stimulates areas of the motor cortex and areas of the cerebellum having to do with motor learning is beneficial in aiding mice with Rett syndrome.
A recent study found that adult rats with amblyopia improved visual acuity two weeks after being placed into an enriched environment. The same study showed that another two weeks after ending environmental enrichment, the rats retained their visual acuity improvement. Conversely, rats in a standard environment showed no improvement in visual acuity. It was thus concluded that environmental enrichment reduces GABA inhibition and increases BDNF expression in the visual cortex. As a result, the growth and development of neurons and synapses in the visual cortex were much improved due to the enriched environment.
Studies have shown that with the help of environmental enrichment the effects of sensory deprivation can be corrected. For example, a visual impairment known as "dark-rearing" in the visual cortex can be prevented and rehabilitated. In general, an enriched environment will improve, if not repair, the sensory systems animals possess.
During development, gestation is one of the most critical periods for exposure to any lead. Exposure to high levels of lead at this time can lead to inferior spatial learning performance. Studies have shown that environmental enrichment can overturn damage to the hippocampus induced by lead exposure. Learning and spatial memory that are dependent on the long-term potentiation of the hippocampus are vastly improve as subjects in an enriched environments had lower levels of lead concentration in their hippocampi. The findings also showed that enriched environments result in some natural protection of lead-induced brain deficits.
Chronic spinal cord injuries
Research has indicated that animals suffering from spinal cord injuries showed significant improvement in motor capabilities even with a long delay in treatment after the injury when exposed to environmental enrichment. Social interactions, exercise, and novelty all play major roles in aiding the recovery of an injured subject. This has led to some suggestions that the spinal cord has a continued plasticity and all efforts must be made for enriched environments to stimulate this plasticity in order to aid recovery.
Maternal deprivation stress
Maternal deprivation can be caused by the abandonment by a nurturing parent at a young age. In rodents or nonhuman primates, this leads to a higher vulnerability for stress-related illness. Research suggests that environmental enrichment can reverse the effects of maternal separation on stress reactivity, possibly by affecting the hippocampus and the prefrontal cortex.
In all children, maternal care is one of the significant influences for hippocampal development, providing the foundation for stable and individualized learning and memory. However, this is not the case for those who have experienced child neglect. Researchers determined that through environmental enrichment, a neglected child can partially receive the same hippocampal development and stability, albeit not at the same level as that of the presence of a parent or guardian. The results were comparable to those of child intervention programs, rendering environmental enrichment a useful method for dealing with child neglect.[not in citation given]
Decreased hippocampal neurogenesis is a characteristic of aging. Environmental enrichment increases neurogenesis in aged rodents by potentiating neuronal differentiation and new cell survival. As a result, subjects exposed to environmental enrichment aged better due to superior ability in retaining their levels of spatial and learning memory.
Prenatal and perinatal cocaine exposure
Research has shown that mice exposed to environmental enrichment are less affected by the consequences of cocaine exposure in comparison with those in standard environments. Although the levels of dopamine in the brains of both sets of mice were relatively similar, when both subjects were exposed to the cocaine injection, mice in enriched environment were significantly less responsive than those in standard environments. It was thus concluded that both the activating and rewarding effects are suppressed by environmental enrichment and early exposure to environmental enrichment can help prevent drug addiction.
Though environmental enrichment research has been mostly done upon rodents, similar effects occur in primates, and are likely to affect the human brain. However, direct research upon human synapses and their numbers is limited since this requires histological study of the brain. A link, however, has been found between educational level and greater dendritic branch complexity following autopsy removal of the brain.
Localized cerebral cortex changes
MRI detects localized cerebral cortex expansion after people learn complex tasks such as mirror reading (in this case in the right occipital cortex), three-ball juggling (bilateral mid-temporal area and left posterior intraparietal sulcus), and when medical students intensively revise for exams (bilaterally in the posterior and lateral parietal cortex). Such changes in gray matter volume can be expected to link to changes in synapse numbers due to the increased numbers of glial cells and the expanded capillary vascularization needed to support their increased energy consumption.
Children that receive impoverished stimulation due to being confined to cots without social interaction or reliable caretakers in low quality orphanages show severe delays in cognitive and social development. 12% of them if adopted after 6 months of age show autistic or mildly autistic traits later at four years of age. Some children in such impoverished orphanages at two and half years of age still fail to produce intelligible words, though a year of foster care enabled such children to catch up in their language in most respects. Catch-up in other cognitive functioning also occurs after adoption, though problems continue in many children if this happens after the age of 6 months
Such children show marked differences in their brains, consistent with research upon experiment animals, compared to children from normally stimulating environments. They have reduced brain activity in the orbital prefrontal cortex, amygdala, hippocampus, temporal cortex, and brain stem. They also showed less developed white matter connections between different areas in their cerebral cortices, particularly the uncinate fasciculus.
Conversely, enriching the experience of preterm infants with massage quickens the maturating of their electroencephalographic activity and their visual acuity. Moreover, as with enrichment in experimental animals, this associates with an increase in IGF-1.
Cognitive reserve and resilience
Another source of evidence for the effect of environment stimulation upon the human brain is cognitive reserve (a measure of the brain’s resilience to cognitive impairment) and the level of a person’s education. Not only is higher education linked to a more cognitively demanding educational experience, but it also correlates with a person’s general engagement in cognitively demanding activities. The more education a person has received, the less the effects of aging, dementia, white matter hyperintensities, MRI-defined brain infarcts, Alzheimer's disease, and traumatic brain injury. Also, aging and dementia are less in those that engage in complex cognitive tasks. The cognitive decline of those with epilepsy could also be affected by the level of a person’s education.
- Behavioral enrichment
- Neural development
- Perceptual learning
- Phenotypic plasticity
- Rat Park
- Hebb DO (1947). "The effects of early experience on problem solving at maturity". American Psychologist 2: 306–7.
- Krech D, Rosenzweig MR, Bennett EL (December 1960). "Effects of environmental complexity and training on brain chemistry". J Comp Physiol Psychol 53 (6): 509–19. PMID 13754181. doi:10.1037/h0045402.
- Rosenzweig MR, Krech D, Bennett EL, Diamond MC (August 1962). "Effects of environmental complexity and training on brain chemistry and anatomy: a replication and extension". J Comp Physiol Psychol 55 (4): 429–37. PMID 14494091. doi:10.1037/h0041137.
- Altman J, Das GD (December 1964). "Autoradiographic Examination of the Effects of Enriched Environment on the Rate of Glial Multiplication in the Adult Rat Brain". Nature 204 (4964): 1161–3. PMID 14264369. doi:10.1038/2041161a0.
- Diamond MC, Krech D, Rosenzweig MR (August 1964). "The Effects of an Enriched Environment on the Histology of the Rat Cerebral Cortex". J. Comp. Neurol. 123: 111–20. PMID 14199261. doi:10.1002/cne.901230110.
- Harlow HF, Rowland GL, Griffin GA (December 1964). "The Effect of Total Social Deprivation on the Development of Monkey Behavior". Psychiatr Res Rep Am Psychiatr Assoc 19: 116–35. PMID 14232649.
- Diamond MC, Law F, Rhodes H et al. (September 1966). "Increases in cortical depth and glia numbers in rats subjected to enriched environment". J. Comp. Neurol. 128 (1): 117–26. PMID 4165855. doi:10.1002/cne.901280110.
- Schapiro S, Vukovich KR (January 1970). "Early experience effects upon cortical dendrites: a proposed model for development". Science 167 (3916): 292–4. PMID 4188192. doi:10.1126/science.167.3916.292.
- Bennett EL, Diamond MC, Krech D, Rosenzweig MR (October 1964). "Chemical and Anatomical Plasticity Brain". Science 146 (3644): 610–9. PMID 14191699. doi:10.1126/science.146.3644.610.
- Briones TL, Klintsova AY, Greenough WT (August 2004). "Stability of synaptic plasticity in the adult rat visual cortex induced by complex environment exposure". Brain Res. 1018 (1): 130–5. PMID 15262214. doi:10.1016/j.brainres.2004.06.001.
- Holtmaat AJ, Trachtenberg JT, Wilbrecht L et al. (January 2005). "Transient and persistent dendritic spines in the neocortex in vivo". Neuron 45 (2): 279–91. PMID 15664179. doi:10.1016/j.neuron.2005.01.003.
- Zuo Y, Lin A, Chang P, Gan WB (April 2005). "Development of long-term dendritic brain stability in diverse regions of cerebral cortex". Neuron 46 (2): 181–9. PMID 15848798. doi:10.1016/j.neuron.2005.04.001.
- Greenough WT, Volkmar FR (August 1973). "Pattern of dendritic branching in occipital cortex of rats reared in complex environments". Exp. Neurol. 40 (2): 491–504. PMID 4730268. doi:10.1016/0014-4886(73)90090-3.
- Landi S, Sale A, Berardi N, Viegi A, Maffei L, Cenni MC (January 2007). "Retinal functional development is sensitive to environmental enrichment: a role for BDNF". FASEB J. 21 (1): 130–9. PMID 17135370. doi:10.1096/fj.06-6083com.
- Volkmar FR, Greenough WT (June 1972). "Rearing complexity affects branching of dendrites in the visual cortex of the rat". Science 176 (4042): 1445–7. PMID 5033647. doi:10.1126/science.176.4042.1445.
- Wallace CS, Kilman VL, Withers GS, Greenough WT (July 1992). "Increases in dendritic length in occipital cortex after 4 days of differential housing in weanling rats". Behav. Neural Biol. 58 (1): 64–8. PMID 1417672. doi:10.1016/0163-1047(92)90937-Y.
- Sirevaag AM, Greenough WT (October 1987). "Differential rearing effects on rat visual cortex synapses. III. Neuronal and glial nuclei, boutons, dendrites, and capillaries". Brain Res. 424 (2): 320–32. PMID 3676831. doi:10.1016/0006-8993(87)91477-6.
- Sirevaag AM, Greenough WT (April 1985). "Differential rearing effects on rat visual cortex synapses. II. Synaptic morphometry". Brain Res. 351 (2): 215–26. PMID 3995348. doi:10.1016/0165-3806(85)90193-2.
- Shinohara Y, Hosoya A, Hirase H (April 2013). "Experience enhances gamma oscillations and interhemispheric asymmetry in the hippocampus". Nat Commun 4 (4): 1652. PMID 23552067. doi:10.1038/ncomms2658.
- Jones TA, Greenough WT (January 1996). "Ultrastructural evidence for increased contact between astrocytes and synapses in rats reared in a complex environment". Neurobiol Learn Mem 65 (1): 48–56. PMID 8673406. doi:10.1006/nlme.1996.0005.
- Borowsky IW, Collins RC (October 1989). "Metabolic anatomy of brain: a comparison of regional capillary density, glucose metabolism, and enzyme activities". J. Comp. Neurol. 288 (3): 401–13. PMID 2551935. doi:10.1002/cne.902880304.
- Black JE, Isaacs KR, Anderson BJ, Alcantara AA, Greenough WT (July 1990). "Learning causes synaptogenesis, whereas motor activity causes angiogenesis, in cerebellar cortex of adult rats". Proc. Natl. Acad. Sci. U.S.A. 87 (14): 5568–72. PMC 54366. PMID 1695380. doi:10.1073/pnas.87.14.5568.
- Kleim JA, Hogg TM, VandenBerg PM, Cooper NR, Bruneau R, Remple M (January 2004). "Cortical synaptogenesis and motor map reorganization occur during late, but not early, phase of motor skill learning". J. Neurosci. 24 (3): 628–33. PMID 14736848. doi:10.1523/JNEUROSCI.3440-03.2004.
- Sale A, Cenni MC, Ciucci F, Putignano E, Chierzi S, Maffei L (2007). Reh, Thomas, ed. "Maternal Enrichment during Pregnancy Accelerates Retinal Development of the Fetus". PLoS ONE 2 (11): e1160. PMC 2063464. PMID 18000533. doi:10.1371/journal.pone.0001160. open access publication - free to read
- Fan Y, Liu Z, Weinstein PR, Fike JR, Liu J (January 2007). "Environmental enrichment enhances neurogenesis and improves functional outcome after cranial irradiation". Eur. J. Neurosci. 25 (1): 38–46. PMID 17241265. doi:10.1111/j.1460-9568.2006.05269.x.
- Veena J, Srikumar BN, Mahati K, Bhagya V, Raju TR, Shankaranarayana Rao BS (March 2009). "Enriched environment restores hippocampal cell proliferation and ameliorates cognitive deficits in chronically stressed rats". J. Neurosci. Res. 87 (4): 831–43. PMID 19006089. doi:10.1002/jnr.21907.
- Meshi D, Drew MR, Saxe M et al. (June 2006). "Hippocampal neurogenesis is not required for behavioral effects of environmental enrichment". Nat. Neurosci. 9 (6): 729–31. PMID 16648847. doi:10.1038/nn1696.
- Rampon C, Jiang CH, Dong H et al. (November 2000). "Effects of environmental enrichment on gene expression in the brain". Proc. Natl. Acad. Sci. U.S.A. 97 (23): 12880–4. PMC 18858. PMID 11070096. doi:10.1073/pnas.97.23.12880.
- Ickes BR, Pham TM, Sanders LA, Albeck DS, Mohammed AH, Granholm AC (July 2000). "Long-term environmental enrichment leads to regional increases in neurotrophin levels in rat brain". Exp. Neurol. 164 (1): 45–52. PMID 10877914. doi:10.1006/exnr.2000.7415.
- Torasdotter M, Metsis M, Henriksson BG, Winblad B, Mohammed AH (June 1998). "Environmental enrichment results in higher levels of nerve growth factor mRNA in the rat visual cortex and hippocampus". Behav. Brain Res. 93 (1–2): 83–90. PMID 9659990. doi:10.1016/S0166-4328(97)00142-3.
- Zhu SW, Codita A, Bogdanovic N et al. (February 2009). "Influence of environmental manipulation on exploratory behaviour in male BDNF knockout mice". Behav. Brain Res. 197 (2): 339–46. PMID 18951926. doi:10.1016/j.bbr.2008.09.032.
- Rasmuson S, Olsson T, Henriksson BG et al. (January 1998). "Environmental enrichment selectively increases 5-HT1A receptor mRNA expression and binding in the rat hippocampus". Brain Res. Mol. Brain Res. 53 (1–2): 285–90. PMID 9473697. doi:10.1016/S0169-328X(97)00317-3.
- Escorihuela RM, Fernández-Teruel A, Tobeña A et al. (July 1995). "Early environmental stimulation produces long-lasting changes on beta-adrenoceptor transduction system". Neurobiol Learn Mem 64 (1): 49–57. PMID 7582812. doi:10.1006/nlme.1995.1043.
- Nithianantharajah J, Levis H, Murphy M (May 2004). "Environmental enrichment results in cortical and subcortical changes in levels of synaptophysin and PSD-95 proteins". Neurobiol Learn Mem 81 (3): 200–10. PMID 15082021. doi:10.1016/j.nlm.2004.02.002.
- Gogolla N, Galimberti I, Deguchi Y, Caroni P (May 2009). "Wnt signaling mediates experience-related regulation of synapse numbers and mossy fiber connectivities in the adult hippocampus". Neuron 62 (4): 510–25. PMID 19477153. doi:10.1016/j.neuron.2009.04.022.
- During MJ, Cao L (February 2006). "VEGF, a mediator of the effect of experience on hippocampal neurogenesis". Curr Alzheimer Res 3 (1): 29–33. PMID 16472200. doi:10.2174/156720506775697133.
- Woo CC, Leon M (March 2011). "Environmental Enrichment as an Effective Treatment for Autism: A Randomized Controlled Trial". Behav Neurosci 72 (3): 406–11. PMID 21208598. doi:10.1037/a0033010.
- Berardi N, Braschi C, Capsoni S, Cattaneo A, Maffei L (June 2007). "Environmental enrichment delays the onset of memory deficits and reduces neuropathological hallmarks in a mouse model of Alzheimer-like neurodegeneration". J. Alzheimers Dis. 11 (3): 359–70. PMID 17851186.
- Spires TL, Grote HE, Varshney NK et al. (March 2004). "Environmental enrichment rescues protein deficits in a mouse model of Huntington's disease, indicating a possible disease mechanism". J. Neurosci. 24 (9): 2270–6. PMID 14999077. doi:10.1523/JNEUROSCI.1658-03.2004.
- Faherty CJ, Raviie Shepherd K, Herasimtschuk A, Smeyne RJ (March 2005). "Environmental enrichment in adulthood eliminates neuronal death in experimental Parkinsonism". Brain Res. Mol. Brain Res. 134 (1): 170–9. PMID 15790541. doi:10.1016/j.molbrainres.2004.08.008.
- Goldberg, NR; Fields, V; Pflibsen, L; Salvatore, MF; Meshul, CK (March 2012). "Social enrichment attenuates nigrostriatal lesioning and reverses motor impairment in a progressive 1-methyl-2-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease.". Neurobiology of disease 45 (3): 1051–67. PMID 22198503. doi:10.1016/j.nbd.2011.12.024.
- Janssen, H.; Bernhardt, J.; Collier, J. M.; Sena, E. S.; McElduff, P.; Attia, J.; Pollack, M.; Howells, D. W.; Nilsson, M.; Calford, M. B.; Spratt, N. J. (12 September 2010). "An Enriched Environment Improves Sensorimotor Function Post-Ischemic Stroke". Neurorehabilitation and Neural Repair 24 (9): 802–813. PMID 20834046. doi:10.1177/1545968310372092.
- Janssen, Heidi; Ada, Louise; Bernhardt, Julie; McElduff, Patrick; Pollack, Michael; Nilsson, Michael; Spratt, Neil J. (29 April 2013). "An enriched environment increases activity in stroke patients undergoing rehabilitation in a mixed rehabilitation unit: a pilot non-randomized controlled trial". Disability and Rehabilitation 36 (3): 1–8. PMID 23627534. doi:10.3109/09638288.2013.788218.
- Kondo M, Gray LJ, Pelka GJ, Christodoulou J, Tam PP, Hannan AJ (June 2008). "Environmental enrichment ameliorates a motor coordination deficit in a mouse model of Rett syndrome--Mecp2 gene dosage effects and BDNF expression". Eur. J. Neurosci. 27 (12): 3342–50. PMID 18557922. doi:10.1111/j.1460-9568.2008.06305.x.
- Sale A, Maya Vetencourt JF, Medini P et al. (June 2007). "Environmental enrichment in adulthood promotes amblyopia recovery through a reduction of intracortical inhibition". Nat. Neurosci. 10 (6): 679–81. PMID 17468749. doi:10.1038/nn1899.
- Argandoña EG, Bengoetxea H, Lafuente JV. (2009). "Physical exercise is required for environmental enrichment to offset the quantitative effects of dark-rearing on the S-100β astrocytic density in the rat visual cortex". Journal of Anatomy 215 (2): 132–140. PMC 2740960. PMID 19500177. doi:10.1111/j.1469-7580.2009.01103.x.
- Cao, Xiujing; Huang, Shenghai; Ruan, Diyun (April 2008). "Enriched environment restores impaired hippocampal long-term potentiation and water maze performance induced by developmental lead exposure in rats". Developmental Psychobiology 50 (3): 307–313. doi:10.1002/dev.20287.
- Fischer FR, Peduzzi JD (2007). "Functional Recovery in Rats With Chronic Spinal Cord Injuries After Exposure to an Enriched Environment". J Spinal Cord Med 30 (2): 147–55. PMC 2031947. PMID 17591227.
- Francis DD, Diorio J, Plotsky PM, Meaney MJ (September 2002). "Environmental enrichment reverses the effects of maternal separation on stress reactivity". J. Neurosci. 22 (18): 7840–3. PMID 12223535.
- Bredy TW, Humpartzoomian RA, Cain DP, Meaney MJ (2003). "Partial reversal of the effect of maternal care on cognitive function through environmental enrichment". Neuroscience 118 (2): 571–6. PMID 12699791. doi:10.1016/S0306-4522(02)00918-1.
- Speisman, RB; Kumar, A; Rani, A; Pastoriza, JM; Severance, JE; Foster, TC; Ormerod, BK (January 2013). "Environmental enrichment restores neurogenesis and rapid acquisition in aged rats.". Neurobiology of Aging 34 (1): 263–74. PMID 22795793. doi:10.1016/j.neurobiolaging.2012.05.023.
- Solinas M, Thiriet N, El Rawas R, Lardeux V, Jaber M (April 2009). "Environmental enrichment during early stages of life reduces the behavioral, neurochemical, and molecular effects of cocaine". Neuropsychopharmacology 34 (5): 1102–11. PMID 18463628. doi:10.1038/npp.2008.51.
- Kozorovitskiy Y, Gross CG, Kopil C et al. (November 2005). "Experience induces structural and biochemical changes in the adult primate brain". Proc. Natl. Acad. Sci. U.S.A. 102 (48): 17478–82. PMC 1297690. PMID 16299105. doi:10.1073/pnas.0508817102.
- Jacobs B, Schall M, Scheibel AB (January 1993). "A quantitative dendritic analysis of Wernicke's area in humans. II. Gender, hemispheric, and environmental factors". J. Comp. Neurol. 327 (1): 97–111. PMID 8432910. doi:10.1002/cne.903270108.
- Ilg R, Wohlschläger AM, Gaser C et al. (April 2008). "Gray matter increase induced by practice correlates with task-specific activation: a combined functional and morphometric magnetic resonance imaging study". J. Neurosci. 28 (16): 4210–5. PMID 18417700. doi:10.1523/JNEUROSCI.5722-07.2008.
- Draganski B, Gaser C, Busch V, Schuierer G, Bogdahn U, May A (January 2004). "Neuroplasticity: changes in grey matter induced by training". Nature 427 (6972): 311–2. PMID 14737157. doi:10.1038/427311a.
- Draganski B, Gaser C, Kempermann G et al. (June 2006). "Temporal and spatial dynamics of brain structure changes during extensive learning". J. Neurosci. 26 (23): 6314–7. PMID 16763039. doi:10.1523/JNEUROSCI.4628-05.2006.
- Kaler SR, Freeman BJ (May 1994). "Analysis of environmental deprivation: cognitive and social development in Romanian orphans". J Child Psychol Psychiatry 35 (4): 769–81. PMID 7518826. doi:10.1111/j.1469-7610.1994.tb01220.x.
- Rutter M, Andersen-Wood L, Beckett C et al. (May 1999). "Quasi-autistic patterns following severe early global privation. English and Romanian Adoptees (ERA) Study Team". J Child Psychol Psychiatry 40 (4): 537–49. PMID 10357161. doi:10.1017/S0021963099003935.
- Windsor J, Glaze LE, Koga SF (October 2007). "Language acquisition with limited input: Romanian institution and foster care". J. Speech Lang. Hear. Res. 50 (5): 1365–81. PMID 17905917. doi:10.1044/1092-4388(2007/095).
- Beckett C, Maughan B, Rutter M et al. (2006). "Do the effects of early severe deprivation on cognition persist into early adolescence? Findings from the English and Romanian adoptees study". Child Dev 77 (3): 696–711. PMID 16686796. doi:10.1111/j.1467-8624.2006.00898.x.
- Chugani HT, Behen ME, Muzik O, Juhász C, Nagy F, Chugani DC (December 2001). "Local brain functional activity following early deprivation: a study of postinstitutionalized Romanian orphans". Neuroimage 14 (6): 1290–301. PMID 11707085. doi:10.1006/nimg.2001.0917.
- Eluvathingal TJ, Chugani HT, Behen ME et al. (June 2006). "Abnormal brain connectivity in children after early severe socioemotional deprivation: a diffusion tensor imaging study". Pediatrics 117 (6): 2093–100. PMID 16740852. doi:10.1542/peds.2005-1727.
- Guzzetta A, Baldini S, Bancale A et al. (May 2009). "Massage accelerates brain development and the maturation of visual function". J. Neurosci. 29 (18): 6042–51. PMID 19420271. doi:10.1523/JNEUROSCI.5548-08.2009.
- Wilson R, Barnes L, Bennett D (August 2003). "Assessment of lifetime participation in cognitively stimulating activities". J Clin Exp Neuropsychol 25 (5): 634–42. PMID 12815501. doi:10.1076/jcen.25.5.634.14572.
- Corral M, Rodríguez M, Amenedo E, Sánchez JL, Díaz F (2006). "Cognitive reserve, age, and neuropsychological performance in healthy participants". Dev Neuropsychol 29 (3): 479–91. PMID 16671863. doi:10.1207/s15326942dn2903_6.
- Fritsch T, McClendon MJ, Smyth KA, Lerner AJ, Friedland RP, Larsen JD (June 2007). "Cognitive functioning in healthy aging: the role of reserve and lifestyle factors early in life". Gerontologist 47 (3): 307–22. PMID 17565095. doi:10.1093/geront/47.3.307.
- Hall CB, Derby C, LeValley A, Katz MJ, Verghese J, Lipton RB (October 2007). "Education delays accelerated decline on a memory test in persons who develop dementia". Neurology 69 (17): 1657–64. PMID 17954781. doi:10.1212/01.wnl.0000278163.82636.30.
- Nebes RD, Meltzer CC, Whyte EM et al. (2006). "The relation of white matter hyperintensities to cognitive performance in the normal old: education matters". Neuropsychol Dev Cogn B Aging Neuropsychol Cogn 13 (3–4): 326–40. PMID 16887777. doi:10.1080/138255890969294.
- Elkins JS, Longstreth WT, Manolio TA, Newman AB, Bhadelia RA, Johnston SC (August 2006). "Education and the cognitive decline associated with MRI-defined brain infarct". Neurology 67 (3): 435–40. PMID 16894104. doi:10.1212/01.wnl.0000228246.89109.98.
- Koepsell TD, Kurland BF, Harel O, Johnson EA, Zhou XH, Kukull WA (May 2008). "Education, cognitive function, and severity of neuropathology in Alzheimer disease". Neurology 70 (19 Pt 2): 1732–9. PMID 18160675. doi:10.1212/01.wnl.0000284603.85621.aa.
- Roe CM, Mintun MA, D'Angelo G, Xiong C, Grant EA, Morris JC (November 2008). "Alzheimer's and Cognitive Reserve: Education Effect Varies with 11CPIB Uptake". Arch. Neurol. 65 (11): 1467–71. PMC 2752218. PMID 19001165. doi:10.1001/archneur.65.11.1467.
- Kesler SR, Adams HF, Blasey CM, Bigler ED (2003). "Premorbid intellectual functioning, education, and brain size in traumatic brain injury: an investigation of the cognitive reserve hypothesis". Appl Neuropsychol 10 (3): 153–62. PMID 12890641. doi:10.1207/S15324826AN1003_04.
- Fratiglioni L, Paillard-Borg S, Winblad B (June 2004). "An active and socially integrated lifestyle in late life might protect against dementia". Lancet Neurol 3 (6): 343–53. PMID 15157849. doi:10.1016/S1474-4422(04)00767-7.
- Pai MC, Tsai JJ (2005). "Is cognitive reserve applicable to epilepsy? The effect of educational level on the cognitive decline after onset of epilepsy". Epilepsia 46 (Suppl 1): 7–10. PMID 15816971. doi:10.1111/j.0013-9580.2005.461003.x.
- Diamond, Marian Cleeves (1988). Enriching Heredity: The Impact of the Environment on the Anatomy of the Brain. New York: Free Press. ISBN 978-0-02-907431-2.
- Jensen, Eric (2006). Enriching the Brain: How to maximize every learner's potential. San Francisco: Jossey-Bass, A John Wiley & Sons Imprint. ISBN 978-0-7879-7547-0.
- Renner, M. J. Rosenzweig, M. R. (1987). Enriched and Impoverished Environments: Effects on Brain and Behavior. New York: Springer-Verlag. ISBN 978-3-540-96523-7.