Aerobic Exercise as a Tool to Improve Hippocampal Plasticity and Function in Humans: Practical Implications for Mental Health Treatment

In the paper

“Meta-analyses have found AE interventions to improve cognitive performance across a variety of domains, including attention, executive functioning, processing speed, motor functioning, and memory in healthy young and middle aged adults (Etnier et al., 1997; Smith et al., 2010; Chang et al., 2012;”

What the sources say

• ?Could not verify

  The indexed copy’s Abstract and Working memory paradigm section describe a study of dopamine-related genes and working-memory brain activity, not an exercise meta-analysis. Searches for aerobic-exercise interventions and cognitive outcomes returned no passage addressing the claimed improvement. The supplied title and 1997 attribution also do not match the text associated with the supplied DOI. (LLM, conf=0.78)

  cites Etnier et al., 1997 sourceExperimental — accuracy not yet measured
• Partly supported

  The Abstract Results and Discussion report modest improvements in attention and processing speed, executive function, and memory. But the Discussion describes the finding chiefly for healthy older adults, not specifically healthy young and middle-aged adults. It attributes improvement in motor function to a previous meta-analysis rather than reporting motor function as a result of its own analysis (Discussion; page numbers unavailable). (LLM, conf=0.88)

  cites Smith et al., 2010 sourceExperimental — accuracy not yet measured
• Partly supported

  The Discussion reports an overall cognitive benefit from acute exercise, and §2.7.2 reports positive effects for young-adult and adult samples. Section 2.7.4 finds improvements on some attention, executive-function, information-processing, reaction-time, and memory tasks, but also negative or nonsignificant effects on others. The paper therefore does not establish improvement across every named domain, particularly motor functioning, and its findings concern acute exercise rather than exercise interventions generally. (LLM, conf=0.86)

  cites Chang et al., 2012 sourceExperimental — accuracy not yet measured

In the paper

“Interestingly, AE is specifically associated with an increase the density of small, rather than large-diameter blood vessels in both humans (Bullitt et al., 2009) and animals (Bloor, 2005; Van der Borght et al., 2009).”

What the sources say

• Supported

  The Results report that aerobically active older adults had more small cerebral vessels (radius <0.6 mm), with significant differences in several regions, while vessel counts in larger-radius bins did not differ significantly. Bullitt et al. are cited for the human finding; the animal finding is attributed to other sources. (LLM, conf=0.91)

  cites Bullitt et al., 2009 source
• Not checked yetcites Bloor, 2005 source
• Not checked yetcites Van der Borght et al., 2009 source

In the paper

“One brain region with a high degree of endogenous neuroplasticity is the hippocampus (Bavelier and Neville, 2002).”

What the sources say

• Not checked yetcites Bavelier and Neville, 2002 source

In the paper

“Given its general benefits to ones physical health, low risk profile and relative ease of implementation, AE represents a promising therapeutic target for a range of brain pathologies.”

In the paper

“Some RCTs have stipulated that AE influences divergent cognitive domains, whereas others have suggested AE had no significant impact on cognition at all (Etnier et al., 2006; van Uffelen et al., 2008; Snowden et al., 2011; Gates et al., 2013; Kelly et al., 2014; Young et al., 2015).”

What the sources say

• Not checked yetcites Etnier et al., 2006 source
• Not checked yetcites van Uffelen et al., 2008 source
• Not checked yetcites Gates et al., 2013 source

In the paper

“AE has been suggested as a promising approach in remediating hippocampal harm and cognitive deficits caused by neurodegenerative disorders like AD (Intlekofer and Cotman, 2013), but AE may also be a promising approach for various psychiatric disorders like schizophrenia or MDD (Oertel-Knöchel et al., 2014).”

What the sources say

• Not checked yetcites Oertel-Knöchel et al., 2014 source

In the paper

“On a neural level, findings have been consistent in demonstrating that AE has a strong, positive influence on the structure of the hippocampus, which is not seen to the same extent in any other brain regions (Gomez-Pinilla and Hillman, 2013).”

What the sources say

• Not checked yetcites Gomez-Pinilla and Hillman, 2013

In the paper

“The available evidence strongly suggests that AE has a positive influence on cognition in individuals of all age groups, particularly in older adults.”

In the paper

“as well as in older individuals with mild cognitive impairments or dementia (Heyn et al., 2004; van Uffelen et al., 2008; Gates et al., 2013).”

What the sources say

• Not checked yetcites Heyn et al., 2004 source
• Not checked yetcites van Uffelen et al., 2008 source
• Not checked yetcites Gates et al., 2013 source

In the paper

“Interestingly, a stimulus as peripheral as aerobic exercise (AE) has been demonstrated to have a strong influence on inducing neuroplasticity (Voss et al., 2013a) and promoting cognitive performance (Smith et al., 2010).”

What the sources say

• Not checked yetcites Voss et al., 2013a

In the paper

“The capacity to promote cognitive performance in this way implies that AE may have an important clinical relevance in counteracting the cognitive decline associated with aging or dementia (Kramer et al., 2006) and has catalyzed its systematic investigation.”

What the sources say

• Not checked yetcites Kramer et al., 2006 source

In the paper

“The hippocampus plays an important role in both learning and memory (Jarrard, 1993) and affective processing (Phillips et al., 2003).”

What the sources say

• Not checked yetcites Jarrard, 1993 source

In the paper

“Conversely, the positive influence of AE on neuroplasticity is more pronounced within the hippocampus than in any other brain region (Gomez-Pinilla and Hillman, 2013).”

What the sources say

• Not checked yetcites Gomez-Pinilla and Hillman, 2013

In the paper

“As will be discussed below, it has been extensively demonstrated in animal models that AE stimulates a cascade of neuroplastic mechanisms within the hippocampus that are often paralleled by functional improvements (Voss et al., 2013a; Opendak and Gould, 2015).”

What the sources say

• Not checked yetcites Voss et al., 2013a
• Not checked yetcites Opendak and Gould, 2015

In the paper

“Such inconsistencies may partially be explained by the methodological variation between RCTs, making it difficult to systematically compare their findings in meta-analyses (Angevaren et al., 2008; Young et al., 2015).”

What the sources say

• Not checked yetcites Angevaren et al., 2008 source
• Not checked yetcites Young et al., 2015 source

In the paper

“Interestingly, a stimulus as peripheral as aerobic exercise (AE) has been demonstrated to have a strong influence on inducing neuroplasticity (Voss et al., 2013a) and promoting cognitive performance (Smith et al., 2010).”

What the sources say

• Not checked yetcites Smith et al., 2010 source

In the paper

“To some extent, brain disorders can be considered maladies of neuroplasticity (Krystal et al., 2009).”

What the sources say

• Not checked yetcites Krystal et al., 2009 source

In the paper

“AE has been suggested as a promising approach in remediating hippocampal harm and cognitive deficits caused by neurodegenerative disorders like AD (Intlekofer and Cotman, 2013), but AE may also be a promising approach for various psychiatric disorders like schizophrenia or MDD (Oertel-Knöchel et al., 2014).”

What the sources say

• Not checked yetcites Intlekofer and Cotman, 2013

In the paper

“The hippocampus is heavily involved in learning and memory processes and is particularly vulnerable to damage in various pathological conditions like major depressive disorder (MDD), Alzheimer’s disease and schizophrenia (Adriano et al., 2012; Bartsch and Wulff, 2015; Schmaal et al., 2016).”

What the sources say

• Not checked yetcites Adriano et al., 2012 source
• Not checked yetcites Bartsch and Wulff, 2015
• Not checked yetcites Schmaal et al., 2016 source

In the paper

“Some human studies have focussed on assessing the influence of AE on hippocampus dependent cognition and shown in older adults that AE was associated with improved performances in both episodic (Richards et al., 2003; Stewart et al., 2003; Sabia et al., 2009; Flöel et al., 2010; Ruscheweyh et al., 2011) and spatial (Erickson and Kramer, 2009; Erickson et al., 2010, 2011) memory tasks as well as in”

What the sources say

• Not checked yetcites Déry et al., 2013

In the paper

“Several studies have also shown that hippocampal growth induced by AE correlates with a greater performance on spatial memory tasks such as a virtual Morris Water Maze task (Erickson and Kramer, 2009; Szabo et al., 2011; Herting and Nagel, 2012) and on contextual memory tasks (Chaddock et al., 2010) with correlations ranging from r = 0.12 to r = 0.36.”

What the sources say

• Not checked yetcites Erickson and Kramer, 2009
• Not checked yetcites Szabo et al., 2011 source
• Not checked yetcites Herting and Nagel, 2012

In the paper

“Using hippocampus dependent paradigms, AE has been reliably demonstrated to improve task performance in animal models (van Praag, 2009; Voss et al., 2013a), although this does also depend on others aspects of AE such as the duration and intensity of AE (Naylor et al., 2005; Ploughman et al., 2007; O’Callaghan et al., 2009).”

What the sources say

• Not checked yetcites van Praag, 2009 source
• Not checked yetcites Voss et al., 2013a

In the paper

“Until recently, human studies had primarily focussed on examining the impact of AE on performance in frontal-executive or attentional tasks rather than on specific hippocampus dependent forms of cognition (Ruscheweyh et al., 2011).”

What the sources say

• Not checked yetcites Ruscheweyh et al., 2011 source

In the paper

“Despite a limited selection of studies, these findings indicate that AE may have a positive influence on hippocampus dependent forms of cognition in healthy human participants, similar to what has been consistently shown in animal models.”

In the paper

“Spatial and episodic memory processes are inherently related given their specific reliance on the hippocampus (Bird and Burgess, 2008) and the fact that episodic memories are encoded in a spatio-temporal context (Tulving, 1993), making spatial information important in episodic memory formation.”

What the sources say

• Not checked yetcites Tulving, 1993 source

In the paper

“As there is currently no objective proxy for studying episodic-like memory processing in animals (Templer and Hampton, 2013), hippocampal functioning shall be considered here as a function of contextual and spatial memory task performance when referring to animal literature and episodic and spatial memory task performance in human literature.”

What the sources say

• Not checked yetcites Templer and Hampton, 2013 source

In the paper

“However, some domains of memory are more reliant on hippocampal functioning than others (see Box 1) and therefore, it is possible that the most consistent cognitive improvements may be found in these specific domains of memory.”

In the paper

“A growing body of evidence is also accumulating to suggest that AE may have a prominent impact on hippocampal structure in humans as well as in animal models.”

In the paper

“The human hippocampus plays a vital role in the formation of declarative memories, most prominently of which, in the formation of episodic and spatiotemporal memories (Burgess et al., 2002).”

What the sources say

• Not checked yetcites Burgess et al., 2002 source

In the paper

“Moreover, some studies have demonstrated in preadolescent children and young adults that AE is selectively associated with improved performances on contextual (Chaddock et al., 2010, 2011; Monti et al., 2012) and spatial (Stroth et al., 2009; Herting and Nagel, 2012) memory tasks and not with less hippocampus dependent tasks such as attention, verbal memory, or item recognition tasks.”

What the sources say

• Not checked yetcites Chaddock et al., 2010 source
• Not checked yetcites Chaddock et al., 2011 source
• Not checked yetcites Monti et al., 2012 source

In the paper

“Several studies have also shown that hippocampal growth induced by AE correlates with a greater performance on spatial memory tasks such as a virtual Morris Water Maze task (Erickson and Kramer, 2009; Szabo et al., 2011; Herting and Nagel, 2012) and on contextual memory tasks (Chaddock et al., 2010) with correlations ranging from r = 0.12 to r = 0.36.”

In the paper

“Some human studies have focussed on assessing the influence of AE on hippocampus dependent cognition and shown in older adults that AE was associated with improved performances in both episodic (Richards et al., 2003; Stewart et al., 2003; Sabia et al., 2009; Flöel et al., 2010; Ruscheweyh et al., 2011) and spatial (Erickson and Kramer, 2009; Erickson et al., 2010, 2011) memory tasks as well as in”

What the sources say

• Not checked yetcites Erickson and Kramer, 2009
• Not checked yetcites Erickson et al., 2010 source
• Not checked yetcites Erickson et al., 2011 source

In the paper

“The hippocampus plays an important role in both learning and memory (Jarrard, 1993) and affective processing (Phillips et al., 2003).”

What the sources say

• Not checked yetcites Phillips et al., 2003 source

In the paper

“Higher levels of aerobic fitness have been consistently associated with larger hippocampal or temporal lobe volumes in healthy adolescent (Chaddock et al., 2010) and older adults (Colcombe et al., 2003; Bugg and Head, 2011; Head et al., 2012; Niemann et al., 2014).”

What the sources say

• Not checked yetcites Chaddock et al., 2010 source
• Not checked yetcites Colcombe et al., 2003
• Not checked yetcites Bugg and Head, 2011

In the paper

“Using hippocampus dependent paradigms, AE has been reliably demonstrated to improve task performance in animal models (van Praag, 2009; Voss et al., 2013a), although this does also depend on others aspects of AE such as the duration and intensity of AE (Naylor et al., 2005; Ploughman et al., 2007; O’Callaghan et al., 2009).”

What the sources say

• Not checked yetcites Naylor et al., 2005 source
• Not checked yetcites Ploughman et al., 2007 source
• Not checked yetcites O’Callaghan et al., 2009 source

In the paper

“Spatial and episodic memory processes are inherently related given their specific reliance on the hippocampus (Bird and Burgess, 2008) and the fact that episodic memories are encoded in a spatio-temporal context (Tulving, 1993), making spatial information important in episodic memory formation.”

What the sources say

• Not checked yetcites Bird and Burgess, 2008

In the paper

“Several meta-analyses have denoted the tendency for RCTs to report improvements in memory-based task performance following an AE intervention (Colcombe and Kramer, 2003; van Uffelen et al., 2008; Smith et al., 2010; Chang et al., 2012; Roig et al., 2013).”

What the sources say

• Not checked yetcites Colcombe and Kramer, 2003
• Not checked yetcites van Uffelen et al., 2008 source
• Not checked yetcites Smith et al., 2010 source

In the paper

“Also, the hippocampus, and particularly the DG, is crucial in selecting and separating similar events in space and time, and hence pattern separation is a main function attributed to the hippocampus (Yassa and Stark, 2011; Oomen et al., 2013, 2014).”

What the sources say

• Not checked yetcites Yassa and Stark, 2011 source
• Not checked yetcites Oomen et al., 2013 source
• Not checked yetcites Oomen et al., 2014 source

In the paper

“Some human studies have focussed on assessing the influence of AE on hippocampus dependent cognition and shown in older adults that AE was associated with improved performances in both episodic (Richards et al., 2003; Stewart et al., 2003; Sabia et al., 2009; Flöel et al., 2010; Ruscheweyh et al., 2011) and spatial (Erickson and Kramer, 2009; Erickson et al., 2010, 2011) memory tasks as well as in”

What the sources say

• Not checked yetcites Richards et al., 2003 source
• Not checked yetcites Stewart et al., 2003 source
• Not checked yetcites Sabia et al., 2009 source

In the paper

“Several studies have also shown that hippocampal growth induced by AE correlates with a greater performance on spatial memory tasks such as a virtual Morris Water Maze task (Erickson and Kramer, 2009; Szabo et al., 2011; Herting and Nagel, 2012) and on contextual memory tasks (Chaddock et al., 2010) with correlations ranging from r = 0.12 to r = 0.36.”

What the sources say

• Not checked yetcites Chaddock et al., 2010 source

In the paper

“It is important to note that given the requirement of a conscious experience to form an episodic memory, at present episodic memory cannot be directly studied in animals given the lack of behavioral markers for their conscious experience (Clayton et al., 2001).”

What the sources say

• Not checked yetcites Clayton et al., 2001 source

In the paper

“Also, the hippocampus, and particularly the DG, is crucial in selecting and separating similar events in space and time, and hence pattern separation is a main function attributed to the hippocampus (Yassa and Stark, 2011; Oomen et al., 2013, 2014).”

What the sources say

• Not checked yetcites Yassa and Stark, 2011 source

In the paper

“Moreover, some studies have demonstrated in preadolescent children and young adults that AE is selectively associated with improved performances on contextual (Chaddock et al., 2010, 2011; Monti et al., 2012) and spatial (Stroth et al., 2009; Herting and Nagel, 2012) memory tasks and not with less hippocampus dependent tasks such as attention, verbal memory, or item recognition tasks.”

What the sources say

• Not checked yetcites Stroth et al., 2009 source
• Not checked yetcites Herting and Nagel, 2012

In the paper

“The aforementioned studies demonstrate that AE could have a positive influence on hippocampal functioning, but a significantly greater cohort of systematic investigations using human participants will be necessary to outline this relationship on a broader cognitive level.”

In the paper

“Pertaining to its highly neuroplastic nature (Bavelier and Neville, 2002), the hippocampus is particularly vulnerable to structural and functional deterioration in a wide range of neurological and psychiatric disorders (Bartsch and Wulff, 2015).”

What the sources say

• Not checked yetcites Bartsch and Wulff, 2015

In the paper

“AE interventions have also been shown to increase hippocampal volume in patients with mild cognitive impairments (ten Brinke et al., 2015), schizophrenia (Pajonk et al., 2010), and multiple sclerosis (Leavitt et al., 2014).”

What the sources say

• Not checked yetcites Pajonk et al., 2010 source

In the paper

“There is a growing cohort of evidence to suggest that AE is associated with increases in hippocampal gray-matter volume in both healthy and non-healthy individuals (Hötting and Röder, 2013; Hamilton and Rhodes, 2015), and with increases in hippocampal microstructural integrity (Kleemeyer et al., 2015).”

What the sources say

• Not checked yetcites Hötting and Röder, 2013 source
• Not checked yetcites Hamilton and Rhodes, 2015

In the paper

“It has been extensively demonstrated that the process of neurogenesis modifies the excitation of hippocampal neurons (Ikrar et al., 2013).”

What the sources say

• Not checked yetcites Ikrar et al., 2013 source

In the paper

“Without information relating to the specific substrates underlying changes in tissue composition, it is difficult to determine the exact functional significance of a change in volume (Czéh and Lucassen, 2007; Thomas et al., 2012; Biedermann et al., 2016).”

What the sources say

• Not checked yetcites Czéh and Lucassen, 2007
• Not checked yetcites Thomas et al., 2012 source
• Not checked yetcites Biedermann et al., 2016 source

In the paper

“White-matter alterations may also occur in non-healthy individuals as one recent RCT demonstrated a 6-month AE intervention to improve global white-matter integrity in patients with schizophrenia (Svatkova et al., 2015).”

What the sources say

• Not checked yetcites Svatkova et al., 2015 source

In the paper

“In some cases, these AE-induced gray-matter changes have been directly correlated with improvements in hippocampal functioning (Prakash et al., 2015).”

What the sources say

• Not checked yetcites Prakash et al., 2015 source

In the paper

“In addition, one RCT that assessed a 12-month AE intervention did demonstrate that greater changes in aerobic fitness were associated with greater improvements in temporal lobe white-matter integrity in healthy, older adults (Voss et al., 2013b).”

What the sources say

• Not checked yetcites Voss et al., 2013b

In the paper

“RCTs in healthy samples have demonstrated that AE interventions were associated with increases in hippocampal volume in young and middle aged (Thomas et al., 2016) and older adults (Colcombe et al., 2006; Erickson et al., 2011; Niemann et al., 2014; Kleemeyer et al., 2015; Maass et al., 2015; Sexton et al., 2015a).”

What the sources say

• Not checked yetcites Colcombe et al., 2006 source
• Not checked yetcites Erickson et al., 2011 source
• Not checked yetcites Niemann et al., 2014 source

In the paper

“The proliferation of adult-born granule cells is thought to play an important role in hippocampal functioning (Deng et al., 2010; Oomen et al., 2014).”

What the sources say

• Not checked yetcites Deng et al., 2010 source
• Not checked yetcites Oomen et al., 2014 source

In the paper

“The subgranular zone of the hippocampal dentate gyrus (DG) is one of the just two primary locations where neurogenesis is known to occur in the adult rodent and human brain (Spalding et al., 2013; Kempermann et al., 2015).”

What the sources say

• Not checked yetcites Spalding et al., 2013 source
• Not checked yetcites Kempermann et al., 2015

In the paper

“In some cases the AE induced growth in hippocampal volume was correlated with improved performances on a computerized spatial memory task (r = 0.28; Erickson et al., 2011) or on a complex figure test of spatial object recognition (r = 0.37; Maass et al., 2015).”

What the sources say

• Not checked yetcites Erickson et al., 2011 source

In the paper

“A recent systematic review concluded that AE was associated with global and localized improvements in white-matter volume and microstructural integrity in older adults (Sexton et al., 2015b).”

What the sources say

• Not checked yetcites Sexton et al., 2015b

In the paper

“In some cases the AE induced growth in hippocampal volume was correlated with improved performances on a computerized spatial memory task (r = 0.28; Erickson et al., 2011) or on a complex figure test of spatial object recognition (r = 0.37; Maass et al., 2015).”

What the sources say

• Not checked yetcites Maass et al., 2015 source

In the paper

“AE interventions have also been shown to increase hippocampal volume in patients with mild cognitive impairments (ten Brinke et al., 2015), schizophrenia (Pajonk et al., 2010), and multiple sclerosis (Leavitt et al., 2014).”

What the sources say

• Not checked yetcites Leavitt et al., 2014 source

In the paper

“AE interventions have also been shown to increase hippocampal volume in patients with mild cognitive impairments (ten Brinke et al., 2015), schizophrenia (Pajonk et al., 2010), and multiple sclerosis (Leavitt et al., 2014).”

What the sources say

• Not checked yetcites ten Brinke et al., 2015 source

In the paper

“These studies support the idea that AE may be beneficial to hippocampal integrity but it is important to note that these human imaging techniques may only directly assess macro-scale changes and not the functional changes or biological mechanisms that may underlie these changes.”

In the paper

“AE appears to have a beneficial impact on global white-matter integrity (Sexton et al., 2015b) and potentially on hippocampal connectivity.”

What the sources say

• Not checked yetcites Sexton et al., 2015b

In the paper

“While some RCTs have found that AE did not have an impact on hippocampal volume (Ruscheweyh et al., 2011; Scheewe et al., 2013; Krogh et al., 2014; Rosenbaum et al., 2015; Malchow et al., 2016), it is possible that such discrepancies are caused by a lack of consistency in AE protocols used (Prakash et al., 2015) or in the methods of calculating hippocampal volume (Niemann et al., 2014).”

What the sources say

• Not checked yetcites Ruscheweyh et al., 2011 source
• Not checked yetcites Scheewe et al., 2013 source
• Not checked yetcites Krogh et al., 2014 source

In the paper

“However, some studies have found AE to be associated with greater white-matter volume in the temporal lobes that surround the hippocampus in older adults (Colcombe et al., 2003, 2006; Tseng et al., 2013; Burzynska et al., 2014).”

What the sources say

• Not checked yetcites Colcombe et al., 2003
• Not checked yetcites Colcombe et al., 2006 source
• Not checked yetcites Tseng et al., 2013 source

In the paper

“There is a growing cohort of evidence to suggest that AE is associated with increases in hippocampal gray-matter volume in both healthy and non-healthy individuals (Hötting and Röder, 2013; Hamilton and Rhodes, 2015), and with increases in hippocampal microstructural integrity (Kleemeyer et al., 2015).”

What the sources say

• Not checked yetcites Kleemeyer et al., 2015 source

In the paper

“Animal models have demonstrated that the inhibition or ablation of neurogenesis impairs performance on spatial and contextual memory tasks while improved performances on these tasks are seen when neurogenesis is stimulated (Deng et al., 2010; Snyder and Cameron, 2012; Aimone et al., 2014; Vadodaria and Jessberger, 2014; Kent et al., 2015).”

What the sources say

• Not checked yetcites Deng et al., 2010 source
• Not checked yetcites Snyder and Cameron, 2012
• Not checked yetcites Aimone et al., 2014 source

In the paper

“Aerobic exercise has been linked to changes in a range of independent and interdependent mechanisms of neuroplasticity within the hippocampus (for comprehensive reviews, see: van Praag, 2009; Gomez-Pinilla and Hillman, 2013; Voss et al., 2013a; Bolijn and Lucassen, 2015; Opendak and Gould, 2015).”

What the sources say

• Not checked yetcites van Praag, 2009 source
• Not checked yetcites Gomez-Pinilla and Hillman, 2013
• Not checked yetcites Voss et al., 2013a

In the paper

“RCTs in healthy samples have demonstrated that AE interventions were associated with increases in hippocampal volume in young and middle aged (Thomas et al., 2016) and older adults (Colcombe et al., 2006; Erickson et al., 2011; Niemann et al., 2014; Kleemeyer et al., 2015; Maass et al., 2015; Sexton et al., 2015a).”

What the sources say

• Not checked yetcites Thomas et al., 2016 source

In the paper

“AE appears to have a beneficial impact on global white-matter integrity (Sexton et al., 2015b) and potentially on hippocampal connectivity.”

In the paper

“It would be reasonable to expect AE to have a specific impact on hippocampal connectivity, but such findings were not supported in this review (Sexton et al., 2015b).”

What the sources say

• Not checked yetcites Sexton et al., 2015b

In the paper

“Therefore, AE may augment hippocampal memory formation by minimizing the interference between highly similar inputs through increasing the rate of cell proliferation (Déry et al., 2013).”

What the sources say

• Not checked yetcites Déry et al., 2013

In the paper

“Indeed, immature granule cells are particularly suited to participate in the learning process as they have a lower threshold for LTP induction (Schmidt-Hieber et al., 2004) and demonstrate enhanced LTP compared to surrounding mature granule cells (Lee S.W. et al., 2012).”

What the sources say

• Not checked yetcites Schmidt-Hieber et al., 2004 source

In the paper

“Animal models have demonstrated that the inhibition or ablation of neurogenesis impairs performance on spatial and contextual memory tasks while improved performances on these tasks are seen when neurogenesis is stimulated (Deng et al., 2010; Snyder and Cameron, 2012; Aimone et al., 2014; Vadodaria and Jessberger, 2014; Kent et al., 2015).”

What the sources say

• Not checked yetcites Deng et al., 2010 source
• Not checked yetcites Snyder and Cameron, 2012
• Not checked yetcites Aimone et al., 2014 source

In the paper

“While there is still debate as to the exact role that adult-born granule cells play in hippocampal functioning, the process of neurogenesis forms a substrate for experience-dependent change (Opendak and Gould, 2015; Lucassen and Oomen, 2016), which has been implicated in fear and anxiety and depression like-behavior (Sahay and Hen, 2007; Besnard and Sahay, 2015; Lucassen et al., 2015; Hu et al., 2”

What the sources say

• Not checked yetcites Opendak and Gould, 2015
• Not checked yetcites Lucassen and Oomen, 2016

In the paper

“Stimulating neurogenesis and promoting DG function is one mechanism through which AE may promote hippocampal function and some recent findings suggest this mechanisms may be driving the macro-scale increases in hippocampal volume found in human imaging studies (Erickson et al., 2011; Fuss et al., 2014).”

In the paper

“While neurogenesis is a crucial process to the spatiotemporal aspect of hippocampal functioning and is likely to be a key mediator of the hippocampal enhancement stimulated by AE (Cotman et al., 2007), more research is needed to elucidate the exact role that adult-born granule cells play in DG and general hippocampal functioning.”

What the sources say

• Not checked yetcites Cotman et al., 2007 source

In the paper

“The dendrites of granule cells within the DG have been shown to increase in length, complexity, and spine density in response to AE (Eadie et al., 2005; Redila and Christie, 2006) as well as spine density in surrounding pyramidal cells of the entorhinal cortex and CA1 regions (Stranahan et al., 2007).”

What the sources say

• Not checked yetcites Stranahan et al., 2007 source

In the paper

“This primarily occurs through the role that neurogenesis plays in facilitating memory formation by dictating a computational mechanism known as pattern separation (Aimone et al., 2011; Sahay et al., 2011).”

What the sources say

• Not checked yetcites Aimone et al., 2011 source
• Not checked yetcites Sahay et al., 2011 source

In the paper

“Stimulating neurogenesis and promoting DG function is one mechanism through which AE may promote hippocampal function and some recent findings suggest this mechanisms may be driving the macro-scale increases in hippocampal volume found in human imaging studies (Erickson et al., 2011; Fuss et al., 2014).”

What the sources say

• Not checked yetcites Erickson et al., 2011 source
• Not checked yetcites Fuss et al., 2014 source

In the paper

“However, AE also induces a variety of other neuroplastic mechanisms that work both independently and in tandem with neurogenesis to improve hippocampal functioning.”

In the paper

“Pattern separation is an essential mechanism for the DG to efficiently process and store sensory inputs to enable the formation of episodic, contextual or spatial memories (Lazarov and Hollands, 2016), and its importance in AE induced cognitive enhancement is epitomized by correlative studies that manipulate neurogenesis (Kent et al., 2015; Lucassen and Oomen, 2016).”

What the sources say

• Not checked yetcites Lazarov and Hollands, 2016

In the paper

“While neurogenesis is a crucial process to the spatiotemporal aspect of hippocampal functioning and is likely to be a key mediator of the hippocampal enhancement stimulated by AE (Cotman et al., 2007), more research is needed to elucidate the exact role that adult-born granule cells play in DG and general hippocampal functioning.”

What the sources say

• Not checked yetcites Cotman et al., 2007 source

In the paper

“For example, inhibiting the rate of cell proliferation in mice was sufficient to impair pattern separation (Deng et al., 2010) and block AE-induced improvements in spatial (Clark et al., 2009) and contextual (Wojtowicz et al., 2008) memory performance, but only in conditions in which the task required fine spatial discriminations (i.e., where pattern separation was necessary; Creer et al., 2010).”

What the sources say

• Not checked yetcites Deng et al., 2010 source

In the paper

“Furthermore, manipulating the rate of proliferation in rodents has been shown to selectively effect hippocampus dependent task performance, such as in spatial and contextual memory or pattern separation tasks, but not in tasks that are less hippocampus dependent, such as delay conditioning (Gould et al., 1999; Shors et al., 2002; Snyder et al., 2005, 2011; Deng et al., 2009; Sahay et al., 2011;”

What the sources say

• Not checked yetcites Gould et al., 1999 source
• Not checked yetcites Shors et al., 2002 source
• Not checked yetcites Snyder et al., 2005 source

In the paper

“AE also interacts with the glutamatergic system through increasing the expression of N-methyl-D-aspartic acid (NMDA) receptors in the hippocampus (specifically, both NR2A and NR2B subtypes), which contributes toward the synaptic plasticity of the region (Molteni et al., 2002; Farmer et al., 2004).”

What the sources say

• Not checked yetcites Molteni et al., 2002 source
• Not checked yetcites Farmer et al., 2004 source

In the paper

“Learning and memory is reliant upon the efficient communication between neural cells through their synapses and AE is thought to enhance this efficiency through promoting synaptic plasticity in a number of ways (Vivar et al., 2013), such as through facilitating long-term potentiation (LTP).”

What the sources say

• Not checked yetcites Vivar et al., 2013 source

In the paper

“For example, inhibiting the rate of cell proliferation in mice was sufficient to impair pattern separation (Deng et al., 2010) and block AE-induced improvements in spatial (Clark et al., 2009) and contextual (Wojtowicz et al., 2008) memory performance, but only in conditions in which the task required fine spatial discriminations (i.e., where pattern separation was necessary; Creer et al., 2010).”

What the sources say

• Not checked yetcites Clark et al., 2009 source

In the paper

“The dendrites of granule cells within the DG have been shown to increase in length, complexity, and spine density in response to AE (Eadie et al., 2005; Redila and Christie, 2006) as well as spine density in surrounding pyramidal cells of the entorhinal cortex and CA1 regions (Stranahan et al., 2007).”

What the sources say

• Not checked yetcites Eadie et al., 2005 source
• Not checked yetcites Redila and Christie, 2006

In the paper

“While there is still debate as to the exact role that adult-born granule cells play in hippocampal functioning, the process of neurogenesis forms a substrate for experience-dependent change (Opendak and Gould, 2015; Lucassen and Oomen, 2016), which has been implicated in fear and anxiety and depression like-behavior (Sahay and Hen, 2007; Besnard and Sahay, 2015; Lucassen et al., 2015; Hu et al., 2”

What the sources say

• Not checked yetcites Sahay and Hen, 2007 source
• Not checked yetcites Besnard and Sahay, 2015
• Not checked yetcites Lucassen et al., 2015 source

In the paper

“Learning and memory is reliant upon the efficient communication between neural cells through their synapses and AE is thought to enhance this efficiency through promoting synaptic plasticity in a number of ways (Vivar et al., 2013), such as through facilitating long-term potentiation (LTP).”

In the paper

“For example, inhibiting the rate of cell proliferation in mice was sufficient to impair pattern separation (Deng et al., 2010) and block AE-induced improvements in spatial (Clark et al., 2009) and contextual (Wojtowicz et al., 2008) memory performance, but only in conditions in which the task required fine spatial discriminations (i.e., where pattern separation was necessary; Creer et al., 2010).”

What the sources say

• Not checked yetcites Creer et al., 2010 source

In the paper

“For example, inhibiting the rate of cell proliferation in mice was sufficient to impair pattern separation (Deng et al., 2010) and block AE-induced improvements in spatial (Clark et al., 2009) and contextual (Wojtowicz et al., 2008) memory performance, but only in conditions in which the task required fine spatial discriminations (i.e., where pattern separation was necessary; Creer et al., 2010).”

What the sources say

• Not checked yetcites Wojtowicz et al., 2008 source

In the paper

“Indeed, immature granule cells are particularly suited to participate in the learning process as they have a lower threshold for LTP induction (Schmidt-Hieber et al., 2004) and demonstrate enhanced LTP compared to surrounding mature granule cells (Lee S.W. et al., 2012).”

What the sources say

• Not checked yetcites Lee S.W. et al., 2012

In the paper

“The importance of BDNF to hippocampal neuroplasticity is epitomized by animal studies, which have found that the manipulation of BDNF expression directly impacts upon performance in spatial and contextual memory tasks (Linnarsson et al., 1997; Alonso et al., 2002; Heldt et al., 2007; Peters et al., 2010), and also that the downregulation of BDNF inhibits AE induced improvements in spatial memory”

What the sources say

• Not checked yetcites Linnarsson et al., 1997 source
• Not checked yetcites Alonso et al., 2002 source
• Not checked yetcites Heldt et al., 2007 source

In the paper

“Improving cerebral blood flow may be an important mediator of AE induced changes in hippocampal functioning (Christie et al., 2008).”

What the sources say

• Not checked yetcites Christie et al., 2008 source

In the paper

“Similarly, in human models AE has been associated with an increase in BDNF serum (Coelho et al., 2013) with some indication of this up-regulation occurring specifically within the hippocampus (Erickson et al., 2011; Voss et al., 2013a).”

What the sources say

• Not checked yetcites Erickson et al., 2011 source
• Not checked yetcites Voss et al., 2013a

In the paper

“Recent studies have shown that BDNF is required for the pattern separation to occur in memory encoding and consolidation, and specifically that BDNF acts on adult-born granule cells within the DG to facilitate pattern separation (Bekinschtein et al., 2013, 2014).”

What the sources say

• Not checked yetcites Bekinschtein et al., 2013 source
• Not checked yetcites Bekinschtein et al., 2014 source

In the paper

“The importance of BDNF to hippocampal neuroplasticity is epitomized by animal studies, which have found that the manipulation of BDNF expression directly impacts upon performance in spatial and contextual memory tasks (Linnarsson et al., 1997; Alonso et al., 2002; Heldt et al., 2007; Peters et al., 2010), and also that the downregulation of BDNF inhibits AE induced improvements in spatial memory”

What the sources say

• Not checked yetcites Vaynman et al., 2004 source

In the paper

“Brain-derived neurotrophic factor may be the most important factor that is upregulated by AE given its extensive involvement in both synaptic plasticity and neurogenesis (Cotman et al., 2007).”

What the sources say

• Not checked yetcites Cotman et al., 2007 source

In the paper

“In line with the molecules’ interaction with neurogenesis and particularly high concentration within the DG subfield of the hippocampus (Farmer et al., 2004), BDNF may play an important role in pattern separation.”

In the paper

“Neurotrophins are important to the development and maintenance of functioning neural cells in the brain (Barbacid, 1995) and are likely to play a crucial role in mediating the impact of AE on hippocampal neuroplasticity and functioning (Cotman et al., 2007; Voss et al., 2013a; Bolijn and Lucassen, 2015).”

What the sources say

• Not checked yetcites Barbacid, 1995 source

In the paper

“While certain morphological changes enhance synaptic plasticity within the CA1 and entorhinal cortex, AE seems to have a particularly potent impact on the granule cells of the DG.”

In the paper

“Recently, a number of human studies have also demonstrated that the increased BDNF serum levels associated with AE are directly correlated with improved performances in various domains of memory including on spatial memory tasks (Piepmeier and Etnier, 2015).”

What the sources say

• Not checked yetcites Piepmeier and Etnier, 2015

In the paper

“This coincides with studies that have demonstrated a greater cerebral blood flow in the human hippocampus (Pereira et al., 2007; Burdette et al., 2010; Maass et al., 2015), some of which have correlated this increase with improved performance on episodic memory tasks (Pereira et al., 2007; Maass et al., 2015).”

What the sources say

• Not checked yetcites Pereira et al., 2007 source
• Not checked yetcites Maass et al., 2015 source

In the paper

“Neurotrophins are important to the development and maintenance of functioning neural cells in the brain (Barbacid, 1995) and are likely to play a crucial role in mediating the impact of AE on hippocampal neuroplasticity and functioning (Cotman et al., 2007; Voss et al., 2013a; Bolijn and Lucassen, 2015).”

What the sources say

• Not checked yetcites Cotman et al., 2007 source
• Not checked yetcites Voss et al., 2013a
• Not checked yetcites Bolijn and Lucassen, 2015