Most psychological and neurobiological models on the organization of human memory share the long-held dichotomy between short-term (STM) and long-term memory (LTM) (Atkinson and Shiffrin, 1968
; Brown, 1958
; Hebb, 1949
; Peterson and Petersen, 1959
). STM serves storing a limited but immediately accessible amount of information for a shorter time (Brown 1958
, Peterson & Peterson 1959
), whereas LTM may permanently store vast amounts of information, which, however, require specific recall processes to be accessed. It has been assumed that this distinction reflects differences in the way storage is implemented neuronally. LTM seems to be largely implemented by structural features, e.g., long-term potentiation of synaptic efficacy (Laroche, 1994
), structural changes of synaptic boutons, and even the growth of new connections between neurons (Bailey, 1999
; Barkai, 2005
; Ramirez-Amaya et al., 2001
). In contrast, STM seems to be more dependent on functional electro-chemical phenomena, i.e., activation states (Frost et al., 1988
; Schiffmann, 1989
). It should be noted though, that at the ultra-structural level this distinction appears to become blurred as even temporarily circulating information may lead to short-term ultra-structural adaptation (Doubell and Stewart, 1993
). Importantly, both systems (STM and LTM) interact with each other, as STM may be considered the (potential) input into LTM while in turn information from LTM may be retrieved into STM (Atkinson and Shiffrin, 1968
In this context, it has to be mentioned that, particularly over the last years, the terms “STM” and “working memory (WM)” have been used virtually indistinguishably. This stems in part from the apparent lack of an unequivocally accepted distinction between both concepts (Cowan, 2008
). It has been proposed that STM should refer to the pure storage of information, while WM includes (the possibility of) content manipulation and transfer between inputs (e.g., visual or tactile sensory information) and outputs (e.g., manual actions or speech) (Engle et al., 1999
). We consider this tentative distinction as a gradual difference in the degree of manipulation (i.e. the number of different cognitive operations on the stored information) required by the different tasks that tap mnemonic functions across a shorter period of time. In this paper, therefore, the apparently broader term working memory (WM) will be used throughout.
The organization of human WM has long been the topic of psychological models (Atkinson and Shiffrin, 1968
; Hebb, 1949
), with the maybe most influential having been proposed by Baddeley and Hitch (Baddeley and Hitch, 1974
). These authors hypothesized the existence of a central executive controlling the priority of incoming information and their dissemination to two subsystems: the phonological loop, responsible for storing verbal material, and the visuospatial sketchpad, responsible for integrating visual input, spatial information (e.g., locations) and object properties (i.e. colour and size) (Baddeley, 2003b
). Later the concept of an “episodic buffer” was added, forming a limited-capacity system for the ultrashort-term, intermediate storage of incoming sensory information (Baddeley, 2000
; Baddeley, 2003a
). While other models have expanded and modified this view, several key features have remained influential to the present date (Brown et al., 1996b
; Snowling et al., 1991
). In particular, the distinction between spatial and verbal components with specific buffer capacities and the idea of an amodal central executive (Stuss and Knight, 2002
) remains dominant. The central executive is not only considered to control the flow of information to the specific subsystems, but is also thought to play a pivotal role in integrating stored material and executive functions needed for comparison, manipulation or, more generally, the further use of the stored material.
One of the motivations underlying the long-standing efforts to understand the organization of the human WM system is the fact that WM impairments have been described in a large variety of neurological and psychiatric diseases. These deficits often have a considerable impact on the quality of life and the socio-economic status of patients. For example, virtually all forms of dementia show WM deficits (Huntley and Howard, 2010
; Iachini et al., 2009
; Maestu et al., 2011
) as do patients with movement disorders like Parkinson s (Beato et al., 2008
; Gilbert et al., 2005
; Possin et al., 2008
) and Huntington s disease (Huber and Paulson, 1987
; Lemiere et al., 2004
). Interestingly, some WM deficits may be irreversible, (e.g., as part of the debilitating negative symptoms seen in patients with chronic schizophrenia) (Berberian et al., 2009
; Driesen et al., 2008
; Fuller et al., 2009
; Horan et al., 2008
; Yi et al., 2009
), whereas others are only evident in the acute phase of a disease (e.g. in depression; cf. (Christopher and MacDonald, 2005
; Rose and Ebmeier, 2006
). Understanding the neural organization of human WM is therefore not only important from a psychological perspective but may help to unravel the differential pathophysiology of its various impairments.
To date there have been numerous functional neuroimaging studies addressing neural activation patterns associated with WM functions. In spite of this large body of literature, however, there is little agreement on various issues pertaining to the organization of human WM. These include:
- Are effects related to WM task performance per se and effects of increasing WM load represented in the same areas?
- How do representations of verbal and non-verbal material differ from each other, i.e., which brain regions may implement phonological and visuospatial buffers?
- Do different to-be-retained object features (e.g., location vs. identify) or task demands entail differential brain responses?
- Which regions are consistently involved in WM independently of experimental peculiarities?
One of the main reasons for this discrepancy between the large amount of available data and the relatively little knowledge gained from it may be the heterogeneity of tasks used in WM experiments. In particular, over the years, researchers have employed multiple paradigms, of which four have been used most widely: the n-back task, the Sternberg task as well as delayed matching to sample (DMTS) and delayed simple matching tasks. N-back tasks include a consecutive presentation of stimuli, each requiring a decision whether the current one is the same as the previous (1-back) or the second to last (2-back). While in Sternberg tasks a set of stimuli is presented followed by a single probe stimulus requiring the decision whether the probe was part of the set, in DMTS tasks a single stimulus is presented first and has to be recognized afterwards among a set of multiple stimuli. Finally, delayed simple matching tasks entail the presentation of a single stimulus that has to be compared to a second, subsequently presented one. That is, there are already at least four major experimental approaches to examine the neural correlates of WM. This diversity was further enhanced by less common paradigms as well as the fact that researchers employed a large variety of stimuli (e.g. verbal material, natural objects or abstract symbols) and various additional experimental manipulations (such as varying load, retention interval or distraction). Further considering that the results of functional imaging studies strongly depend on the chosen contrast, given the relative nature of neuroimaging signals, it may not surprise that results are diverse and consensus is sparse.
From this short overview, it may not surprise, that there is a very large but also extremely heterogeneous and at times inconsistent body of work related to the neural correlates of working memory. In the present study, we now sought to integrate the current literature on the neural correlates of human WM as identified by functional neuroimaging using quantitative coordinate-based meta-analysis over almost 200 individual experiments. Such synthesis of the available neuroimaging data should help to reach a consensus among the extensive literature and to trace back inconsistencies to variations in the experimental approaches. Using this approach towards an unbiased summary of the literature, we thus strive to identify consistent findings, answer the main questions outlined above and provide an overview on the neural organization of human WM.