Effects of computerized working memory training on neuroplasticity in healthy individuals: A combined neuroimaging and neurotransmitter study

“The MSFG is an important part of the default mode network (DMN), which is active at rest and is involved self-referential thinking, mind wandering, and memory retrieval processes (Buckner et al., 2008; Kim, 2012).”

“The ACC, part of the limbic system (Stevens et al., 2011), is crucial for cognitive control, emotion regulation, and conflict-monitoring (Allman et al., 2001; Botvinick et al., 2004; Bush et al., 2000).”

“The ACC, part of the limbic system (Stevens et al., 2011), is crucial for cognitive control, emotion regulation, and conflict-monitoring (Allman et al., 2001; Botvinick et al., 2004; Bush et al., 2000).”

“(Asplund et al., 2010), social cognition(Weissman et al., 2008), and WM (Owen et al., 2005).”

“Specifically, the medial prefrontal cortex receives 5-HT innervation from the dorsal and medial raphe nuclei, with a high density of 5-HT1a and 5-HT1b receptors (Barnes and Sharp, 1999).”

“…in regions significantly involved in learning and memory processing (Cavallaro, 2008; Vaseghi et al., 2022; Wirth et al., 2017) and is implicated in various cognitive functions, including emotion regulation, learning, and memory (Barnes and Sharp, 1999; Eydipour et al., 2017; Hoyer et al., 1994).”

“ALFF measures the intensity of spontaneous fluctuations in the blood-oxygen-level-dependent (BOLD) signal (Zang et al., 2007) and has been utilized to explore the intrinsic neural activity changes associated with cognitive training (Li et al., 2019). for example, in a study of young adults who…”

“…densities, such as those of serotonin (5HT1a, 5HT1b), dopamine (D2), opioid receptors (MU), and glutamate receptors (NMDA, mGluRs), likely reflect alterations in the intrinsic neural activities within areas related to memory, attention, and sensorimotor functions (Niswender and Conn, 2010).”

“The DSFG located in the dorsal part of the frontal lobe, is implicated in higher cognitive functions, including executive functions (e.g., planning, decision-making, and inhibitory control) (Niendam et al., 2012), attentional control Note: * q 0.05, ** q 0.01, *** q 0.001.”

“These processes can be indirectly measured using functional magnetic resonance imaging (fMRI), which provides macroscopic-level proxies for such changes (Zatorre et al., 2012).”

“Several subtypes of dopamine receptors, such as D1 and D2 receptors, are particularly important in the prefrontal cortex for WM tasks (Papalini et al., 2020; Seamans and Yang, 2004).”

“The running memory task is commonly employed as a measure of updating, a crucial element of executive function (Klingberg, 2010).”

“The ANG in the inferior parietal lobule is involved in language processing, attention, and memory recognition (Heidi et al., 2018; Humphreys et al., 2021; Seghier, 2012).”

“It embodies the capability of the brain to reorganize itself by forming new neural connections (Cramer et al., 2011).”

“NMDA receptor, as glutamate receptors (Vyklicky et al., 2014), plays an integral role in synaptic plasticity, which underlies memory formation (Kandel et al., 2014). mGlu5 receptors, abundant in corticolimbic circuitry, regulate cognitive functions depend on NMDA receptors, including learning and…”

“The ACC, part of the limbic system (Stevens et al., 2011), is crucial for cognitive control, emotion regulation, and conflict-monitoring (Allman et al., 2001; Botvinick et al., 2004; Bush et al., 2000).”

“The ACC, part of the limbic system (Stevens et al., 2011), is crucial for cognitive control, emotion regulation, and conflict-monitoring (Allman et al., 2001; Botvinick et al., 2004; Bush et al., 2000).”

“In addition, WMT might enhance the brain ’ s ability to switch between different networks, such as the DMN and the task-positive networks (involved in focused, goal-oriented tasks) (Spreng et al., 2013).”

“In addition, gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the human cerebral cortex (McCormick, 1989), is linked to various cognitive functions such as WM (Jong et al., 2016).”

“The ROL, located around the sylvian fissure, is associated with phonological processing and speech production (Brown et al., 2005; Veroude et al., 2010).”

“(Asplund et al., 2010), social cognition(Weissman et al., 2008), and WM (Owen et al., 2005).”

“In contrast, the PoCG, a part of the primary somatosensory area (Kropf et al., 2018), is involved in somatic sensations (Roux et al., 2018) and plays a role in somatosensory representation, emotional perception, and memory formation (Cao et al., 2018; Kurth et al., 2000; Luck et al., 2010).”

“After identifying neuroimaging changes using ALFF and VBM analysis, the spatial relationships between these changes and the receptors and transporters densities were examined using the JuSpace toolbox (Dukart et al., 2021) (https://github.com/juryxy/JuSpace).”

“NMDA receptor, as glutamate receptors (Vyklicky et al., 2014), plays an integral role in synaptic plasticity, which underlies memory formation (Kandel et al., 2014). mGlu5 receptors, abundant in corticolimbic circuitry, regulate cognitive functions depend on NMDA receptors, including learning and…”

“It is crucial role for various higher cognitive processes, such as problem-solving, learning, and decision-making (Halford et al., 2007; Swanson, 2004).”

“Dopamine D2 receptors modulate the neural activities associated with WM (Dodds et al., 2009; Wang et al., 2004) and involved in mechanisms underlying WMT and neuroplasticity (Backman and Nyberg, 2013; Wang et al., 2012).”

“Typically, an overactive DMN is linked to inefficiencies in cognitive processing, often seen in aging and certain psychiatric conditions (Christakou et al., 2013; Qin and Basak, 2020).”

“…(Vyklicky et al., 2014), plays an integral role in synaptic plasticity, which underlies memory formation (Kandel et al., 2014). mGlu5 receptors, abundant in corticolimbic circuitry, regulate cognitive functions depend on NMDA receptors, including learning and memory (Homayoun et al., 2004).”

“The left MOG plays a vital role in visual processing (Rotshtein et al., 2007; Tu et al., 2013), including visual object recognition (Yonelinas et al., 2001), integrating visual information with other sensory inputs (Laurent et al., 2009; Ripp et al., 2018), and visual-spatial processing (Mangun et…”

“The SPL plays a role in perception, attention, multisensory integration, and WM (Molenberghs et al., 2007; Passarelli et al., 2021; Wang et al., 2015).”

“The MSFG is an important part of the default mode network (DMN), which is active at rest and is involved self-referential thinking, mind wandering, and memory retrieval processes (Buckner et al., 2008; Kim, 2012).”

“…in visual processing (Rotshtein et al., 2007; Tu et al., 2013), including visual object recognition (Yonelinas et al., 2001), integrating visual information with other sensory inputs (Laurent et al., 2009; Ripp et al., 2018), and visual-spatial processing (Mangun et al., 1997; Tapert et al., 2004).”

“…which acts in most excitatory synapses in the central nervous system (Fonnum, 1993), is particularly noteworthy for its role in learning and memory through the plasticity of channel properties, such as the enhancement of glutamate neurotransmission and gene expression (Barco et al., 2006).”

“The PreCG, which houses the primary motor cortex, is crucial for motor function control (Cooke and Graziano, 2004; Desmurget et al., 2014).”

“The neuro-transmitter maps were obtained from healthy controls in PET/SPECT studies (Alakurtti et al., 2015; Dukart et al., 2018; Hesse et al., 2017; Kaller et al., 2017; Savli et al., 2012), focusing on serotonin receptors (5-HT1a, 5-HT1b, and 5-HT2a), dopamine receptors (D1 and D2),…”

“These receptors play an important role in cognitive processes related to frontal lobe functions, such as attention, executive function, and WM (Carli et al., 2006).”

“In contrast, the PoCG, a part of the primary somatosensory area (Kropf et al., 2018), is involved in somatic sensations (Roux et al., 2018) and plays a role in somatosensory representation, emotional perception, and memory formation (Cao et al., 2018; Kurth et al., 2000; Luck et al., 2010).”

“The SPL plays a role in perception, attention, multisensory integration, and WM (Molenberghs et al., 2007; Passarelli et al., 2021; Wang et al., 2015).”

“Neural plasticity encompassesses a range of acquired or learned changes in neural oscillations, myelin reformation, and synaptogenesis (Chang et al., 2016; Fuchs and Flügge, 2014; Guerra et al., 2018).”

“The neuro-transmitter maps were obtained from healthy controls in PET/SPECT studies (Alakurtti et al., 2015; Dukart et al., 2018; Hesse et al., 2017; Kaller et al., 2017; Savli et al., 2012), focusing on serotonin receptors (5-HT1a, 5-HT1b, and 5-HT2a), dopamine receptors (D1 and D2),…”

“While there is growing evidence supporting the use of WMT on tablet devices, particularly in the context of the n-back task as proposed by Takeuchi et al. (2011), our study opted for computer-based training sessions.”

“It is crucial role for various higher cognitive processes, such as problem-solving, learning, and decision-making (Halford et al., 2007; Swanson, 2004).”

“The neuro-transmitter maps were obtained from healthy controls in PET/SPECT studies (Alakurtti et al., 2015; Dukart et al., 2018; Hesse et al., 2017; Kaller et al., 2017; Savli et al., 2012), focusing on serotonin receptors (5-HT1a, 5-HT1b, and 5-HT2a), dopamine receptors (D1 and D2),…”

“In addition, gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the human cerebral cortex (McCormick, 1989), is linked to various cognitive functions such as WM (Jong et al., 2016).”

“Neural plasticity encompassesses a range of acquired or learned changes in neural oscillations, myelin reformation, and synaptogenesis (Chang et al., 2016; Fuchs and Flügge, 2014; Guerra et al., 2018).”

“The DAT regulates dopamine levels in the synaptic cleft and expresses in a subset of central nervous system neurons, influcing behaviors (Bannon, 2005) and cognitive functions such as attention and WM (Suri et al., 2023).”

“Dopamine D2 receptors modulate the neural activities associated with WM (Dodds et al., 2009; Wang et al., 2004) and involved in mechanisms underlying WMT and neuroplasticity (Backman and Nyberg, 2013; Wang et al., 2012).”

“The ROL, located around the sylvian fissure, is associated with phonological processing and speech production (Brown et al., 2005; Veroude et al., 2010).”

“In contrast, the PoCG, a part of the primary somatosensory area (Kropf et al., 2018), is involved in somatic sensations (Roux et al., 2018) and plays a role in somatosensory representation, emotional perception, and memory formation (Cao et al., 2018; Kurth et al., 2000; Luck et al., 2010).”

“(Asplund et al., 2010), social cognition(Weissman et al., 2008), and WM (Owen et al., 2005).”

“The PreCG, which houses the primary motor cortex, is crucial for motor function control (Cooke and Graziano, 2004; Desmurget et al., 2014).”

“The left MOG plays a vital role in visual processing (Rotshtein et al., 2007; Tu et al., 2013), including visual object recognition (Yonelinas et al., 2001), integrating visual information with other sensory inputs (Laurent et al., 2009; Ripp et al., 2018), and visual-spatial processing (Mangun et…”

“Cognitive training has also been shown to affect other neurotransmitter systems, such as acetylcholine (Rokem and Silver, 2010), which is involved in attention and memory processes.”

“Dopamine D2 receptors modulate the neural activities associated with WM (Dodds et al., 2009; Wang et al., 2004) and involved in mechanisms underlying WMT and neuroplasticity (Backman and Nyberg, 2013; Wang et al., 2012).”

“Similarly, a two-weeks training period with a Go/NoGo task resulted in increase in GMV in the right orbital region of the inferior frontal gyrus (Chavan et al., 2015).”

“…(BOLD) signal (Zang et al., 2007) and has been utilized to explore the intrinsic neural activity changes associated with cognitive training (Li et al., 2019). for example, in a study of young adults who received four weeks of WMT (Takeuchi et al., 2017), fractional ALFF (fALFF) increased…”

“Several subtypes of dopamine receptors, such as D1 and D2 receptors, are particularly important in the prefrontal cortex for WM tasks (Papalini et al., 2020; Seamans and Yang, 2004).”

“A computerized and standardized adaptive running memory task was used to train WM (Zhao et al., 2013).”

“Specifically, serotonin (5-hydroxytryptamine, 5-HT) is an important modulatory neurotransmitter with strong projections from the midbrain and raphe nuclei of the brainstem (Maddaloni et al., 2017).”

“The left MOG plays a vital role in visual processing (Rotshtein et al., 2007; Tu et al., 2013), including visual object recognition (Yonelinas et al., 2001), integrating visual information with other sensory inputs (Laurent et al., 2009; Ripp et al., 2018), and visual-spatial processing (Mangun et…”

“Dopamine D2 receptors modulate the neural activities associated with WM (Dodds et al., 2009; Wang et al., 2004) and involved in mechanisms underlying WMT and neuroplasticity (Backman and Nyberg, 2013; Wang et al., 2012).”

“The utilization of an unadjusted threshold aligns with specific preliminary investigations in neuroimaging (Nenad et al., 2015; Wang et al., 2021; Zhang et al., 2017), while the threshold for a substantial cluster size was chosen to balance the risk of type I and type II errors, controlling for…”

“The excitatory neurotransmitter glutamate, which acts in most excitatory synapses in the central nervous system (Fonnum, 1993), is particularly noteworthy for its role in learning and memory through the plasticity of channel properties, such as the enhancement of glutamate neurotransmission and…”

“Enhanced ALFF in the middle frontal gyrus, superior frontal gyrus, and anterior cerebellum lobe was also observed in healthy older adults following multimodal cognitive traning, with these changes associated with improvements in cognitive performance (Yin et al., 2014).”

“Neuroplasticity is the adaptability of the brain in response to internal and external stimuli (Schverer et al., 2018).”

“…the cognitive demands of WMT. Studies have shown that cognitive training can lead to increases in GMV in brain areas involved in the trained tasks (Brooks et al., 2016; Colom et al., 2016), supporting the idea that the brain remains plastic and capable of morphological changes in response to…”

“Typically, an overactive DMN is linked to inefficiencies in cognitive processing, often seen in aging and certain psychiatric conditions (Christakou et al., 2013; Qin and Basak, 2020).”

“…activity changes associated with cognitive training (Li et al., 2019). for example, in a study of young adults who received four weeks of WMT (Takeuchi et al., 2017), fractional ALFF (fALFF) increased in the right dorsolateral prefrontal cortex, frontopolar region, and medial prefrontal…”

“In contrast, the PoCG, a part of the primary somatosensory area (Kropf et al., 2018), is involved in somatic sensations (Roux et al., 2018) and plays a role in somatosensory representation, emotional perception, and memory formation (Cao et al., 2018; Kurth et al., 2000; Luck et al., 2010).”

“The serotonin family (e.g., 5-HT1a, 5-HT1b, and 5-HT2a) is highly concentrated in regions significantly involved in learning and memory processing (Cavallaro, 2008; Vaseghi et al., 2022; Wirth et al., 2017) and is implicated in various cognitive functions, including emotion regulation, learning,…”

“…in visual processing (Rotshtein et al., 2007; Tu et al., 2013), including visual object recognition (Yonelinas et al., 2001), integrating visual information with other sensory inputs (Laurent et al., 2009; Ripp et al., 2018), and visual-spatial processing (Mangun et al., 1997; Tapert et al., 2004).”

“The previous study provides comprehensive details on these tasks (Ma et al., 2017).”

“…demands of WMT. Studies have shown that cognitive training can lead to increases in GMV in brain areas involved in the trained tasks (Brooks et al., 2016; Colom et al., 2016), supporting the idea that the brain remains plastic and capable of morphological changes in response to cognitive demands.”

“The PoCG, as discussed, is a key for processing somatosensory information (Inoue et al., 2013).”

“…a study on time-compressed speech trainging for approximately four weeks found increased fALFF in the left superior temporal gyrus compared to the active control group in young adults (Maruyama et al., 2018), although no significant differences in cognitive performance measurements were observed.”

“The utilization of an unadjusted threshold aligns with specific preliminary investigations in neuroimaging (Nenad et al., 2015; Wang et al., 2021; Zhang et al., 2017), while the threshold for a substantial cluster size was chosen to balance the risk of type I and type II errors, controlling for…”

“…fast simple numerical calculation (FSNC) training on regional GMV and cerebral blood flow (CBF) in healthy young adults observed that FSNC training improved performance on tasks related to simple processing speed, speeded executive functioning, and arithmetic tasks (Takeuchi et al., 2016).”

“The precentral cortex, primarily involved in motor control and coordination, has been increasingly recognised for its role in working memoryandemotionalregulation 56 .”

“23 walking with cognitive tasks—strengthens connectivity in brain regions associated with attention and executive function.”

“By contrast, computerised working memorytraining(CWMT)standardisesdelivery, capturesprocess-level metrics to quantify realised dose, and adapts dif fi culty in real time 19 .”

“Additionally, computerized working memory training established a relationship between neuroimaging measures and molecular levels in healthy subjects (Fang et al. 2024).”

“…have shown that training on Go/ No-Go tasks and working memory tasks results in increases in gray matter volume (GMV) in the prefrontal cortex [54, 55], providing a macro-level indicator of such changes, though the precise microstructural alterations, time scales, and contributing processes…”

“…the biological mechanisms underlying restorative training-related brain changes in animals and humans, which have demonstrated long-term potentiation and synaptic strengthening, 24,25 enhanced neurogenesis, 26 increased blood fl ow and neurovascular coupling, 24,27 and reduced neuroin fl ammation.”

“…with specific changes in the patterns of hemodynamic response (Spence et al., 2024), supported by studies in the literature showing correlations between both brain structure and function changes after cognitive training protocols (Fang et al., 2024; Haier et al., 2009; Zhang et al., 2025).”

“Similarly, Fang et al. (2024) noted that eight weeks of computerized working memory exercises resulted in notable neurofunctional improvements.”