Neural correlates of training-related working-memory gains in old age Yvonne Brehmer a, ⁎, Anna Rieckmann a , Martin Bellander a , Helena Westerberg a , Håkan Fischer a, b , Lars Bäckman a a Aging Research Center, Karolinska Institute, Stockholm, Sweden b Department of Psychology, Stockholm University, Stockholm, Sweden abstract article info Article history: Received 7 December 2010 Revised 23 May 2011 Accepted 23 June 2011 Available online 2 July 2011 Working memory (WM) functioning declines in old age. Due to its impact on many higher-order cognitive functions, investigating whether training can modify WM performance has recently been of great interest. We examined the relationship between behavioral performance and neural activity following five weeks of intensive WM training in 23 healthy older adults (M= 63.7 years). 12 participants received adaptive training (i.e. individually adjusted task difficulty to bring individuals to their performance maximum), whereas the others served as active controls (i.e. fixed low-level practice). Brain activity was measured before and after training, using fMRI, while subjects performed a WM task under two difficulty conditions. Although there were no training-related changes in WM during scanning, neocortical brain activity decreased post training and these decreases were larger in the adaptive training group than in the controls under high WM load. This pattern suggests intervention-related increases in neural efficiency. Further, there were disproportionate gains in the adaptive training group in trained as well as in non-trained (i.e. attention, episodic memory) tasks assessed outside the scanner, indicating the efficacy of the training regimen. Critically, the degree of training- related changes in brain activity (i.e. neocortical decreases and subcortical increases) was related to the maximum gain score achieved during the intervention period. This relationship suggests that the decreased activity, but also specific activity increases, observed were functionally relevant. © 2011 Elsevier Inc. All rights reserved. Working memory (WM) involves maintaining and manipulating information without the presence of external cues (Baddeley, 2003). WM is critical to several higher-order cognitive abilities, such as fluid intelligence, planning, problem solving, reasoning, and language comprehension (Baddeley, 1992; Engle et al., 1999). Neuronally, WM functioning is dependent on activity in a widespread network, including fronto-striatal, premotor, parietal, and temporal brain regions (D'Esposito et al., 1999; Linden, 2007; Reuter-Lorenz and Sylvester, 2005; Smith and Jonides, 1997; Wager and Smith, 2003; D'Esposito et al., 1999; Linden, 2007; Smith and Jonides, 1997; Wager and Smith, 2003). WM performance, particularly visuospatial WM, declines markedly in old age (Jenkins et al., 2000; Park et al., 2002). This age-related deficit is accompanied by anatomical and neuromodulatory changes, as well as alterations in functional brain activity patterns (Bäckman et al., 2010; Bäckman et al., 2006; Erixon-Lindroth et al., 2005; Nagel et al., 2009, 2010; Rajah and D'Esposito, 2005; Raz, 2005; Reuter-Lorenz, 2000; Reuter-Lorenz and Sylvester, 2005). In recent years, there has been increasing interest in the extent to which WM performance may be enhanced through systematic training. This research demonstrates training-related WM gains in children and younger adults, as well as in persons with acquired brain injuries (Holmes et al., 2009; Jaeggi et al., 2008; Jolles et al., 2010; Klingberg, 2010; Klingberg et al., 2002; Olesen et al., 2004; Thorell et al., 2009; Westerberg et al., 2007). Potential intervention-related benefits in WM and executive functions among older adults have also been examined (Bherer et al., 2006; Dahlin et al., 2008a, 2008b; Erickson et al., 2007; Karbach and Kray, 2009; Li et al., 2008; Mozolic et al., 2009). In general, these studies demonstrate performance improvements in the trained tasks. However, transfer of training gains is typically limited to non- trained tasks from the same domain and not generalizable to tasks tapping non-trained abilities (Buschkuehl et al., 2008; Dahlin et al., 2008a, 2008b; Li et al., 2008, but see Karbach and Kray, 2009; Mahncke et al., 2006; Mozolic et al., 2009). In addition, in these studies a group receiving WM training was compared to a no-contact control group or to a group participating in activities not directly related to WM (e.g., watching movies, walking, listen to educational lectures; e.g., Buschkuehl et al., 2008; Mahncke et al., 2006; Mozolic et al., 2009). This fact makes it difficult to disentangle the effects of the training itself from those that may result from other factors (e.g., motivation, test familiarity, performance anxiety, stimulus–response mappings). With regard to neural correlates of training-related WM gains, an important point concerns whether the intervention results in increases or decreases of brain activity. Whereas increases are thought to reflect individuals' latent potential by recruiting additional brain regions (i.e., additional cortical units or increasing the level of activity within a NeuroImage 58 (2011) 1110–1120 ⁎ Corresponding author at: Aging Research Center, Karolinska Institute, Gävlegatan 16, 11330 Stockholm, Sweden. Fax: +46 8 690 5954. E-mail address: Yvonne.Brehmer@ki.se (Y. Brehmer). 1053-8119/$ – see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.neuroimage.2011.06.079 Contents lists available at ScienceDirect NeuroImage journal homepage: www.elsevier.com/locate/ynimg