Identifying regional activity associated with temporally separated components of working memory using event-related functional MRI

Abstract

This study describes the neural circuitry underlying temporally separated components of working memory (WM) performance-stimulus encoding, maintenance of information during a delay, and the response to a probe. While other studies have applied event-related fMRI to separate epochs of WM tasks, this study differs in that it employs a methodology that does not make any a priori assumptions about the shape of the hemodynamic response (HDR). This is important because no one model of the HDR is valid across the range of activated brain regions and stimulus types. Systematic modeling inaccuracies may lead to the misattribution of activity to adjacent events. Twelve healthy subjects performed a numerical version of the Sternberg Item Recognition Paradigm adapted for rapid presentation event-related fMRI. This paradigm emphasized maintenance rather than manipulative WM processes and used a subcapacity WM load. WM trials with different delay lengths were compared to fixation. The HDR of the entire WM trial for each trial type was estimated using a finite impulse response (FIR). Regional activity associated with the Encode, Delay, and Probe epochs was identified using contrasts that were based on the FIR estimates and by examining the HDRs. Each epoch was associated with a distinct but overlapping pattern of regional activity. Activation of the dorsolateral prefrontal cortex, thalamus, and basal ganglia was exclusively associated with the probe. This suggests that frontostriatal neural circuitry participates in selecting an appropriate response based on the contents of WM.

Functional Imaging of Working Memory after 24 Hr of Total Sleep Deprivation

“…Additionally, we observed greater left dorsomedial thalamus activation with PLUS. Prior working-memory experiments have demonstrated thalamic activation in association with increased working memory demand (Barch et al, 1997;Callicott et al, 1999;Manoach et al, 2003). The increase in thalamic activation in concert with prefrontal activation is consonant with the existence of extensive reciprocal connections between the dorsomedial thalamic nucleus and the prefrontal cortex.…”

Circuitry underlying temporally extended spatial working memory

“…Clusters of significantly active voxels were found in regions frequently identified as contributing to VSWM tasks, including bilateral FEF, right SEF, bilateral anterior inferior parietal lobule, left IPS, right caudate, and left DLPFC (BA 10/46) (e.g., Sweeney et al, 1995Sweeney et al, , 1996McCarthy et al, 1996;Courtney et al, 1997Courtney et al, , 1998Smith and Jonides, 1998;Ungerleider et al, 1998;LaBar et al, 1999;Luna et al, 1999;Cabeza and Nyberg, 2000;Hartley and Speer, 2000;Postle et al, 2000a, b;Rowe et al, 2000;Berman and Colby, 2002;Leung et al, 2002;Manoach et al, 2003;Wager and Smith, 2003;Brown et al, 2004a,b;Curtis et al, 2004Curtis et al, , 2005Passingham and Sakai, 2004;Schluppeck et al, 2005Schluppeck et al, , 2006Curtis and D'Esposito, 2006;Keedy et al, 2006;Klingberg, 2006;Ricciardi et al, 2006;Ranganath, 2006;Postle, 2006;Scherf et al, 2006). The fact that these regions, along with others listed in Table 1, were recruited despite differences in the maintenance duration requirements suggests that they support 'core' components of visual spatial working memory task performance such as encoding, response planning, fundamental aspects of maintenance, and/or the motor response.…”

“…Delay-contingent reductions in firing patterns have also been observed in substantia nigra pars reticulata (SNpr) (Hikosaka and Wurtz, 1983). In humans, numerous neuroimaging studies collectively implicate recruitment of a widely distributed system supporting working memory, including dorsolateral prefrontal cortex (DLPFC), FEF, SEF, intraparietal sulcus (IPS), cingulate cortex, basal ganglia, and lateral cerebellum (e.g., Sweeney et al, 1995Sweeney et al, , 1996McCarthy et al, 1996;Courtney et al, 1997Courtney et al, , 1998Smith and Jonides, 1998;Ungerleider et al, 1998;LaBar et al, 1999;Luna et al, 1999;Cabeza and Nyberg, 2000;Hartley and Speer, 2000;Postle et al, 2000a,b;Rowe et al, 2000;Berman and Colby, 2002;Leung et al, 2002;Manoach et al, 2003;Wager and Smith, 2003;Brown et al, 2004a,b;Curtis et al, 2004Curtis et al, , 2005Passingham and Sakai, 2004;Curtis and D'Esposito, 2006;Keedy et al, 2006;Klingberg, 2006;Ricciardi et al, 2006;Ranganath, 2006;Scherf et al, 2006).…”

Spatiotemporal wavelet analysis for functional MRI

“…This version of the SIRP required subjects to encode a set of target digits, maintain them in working memory (WM) over a fixed period, and to respond to a probe digit by indicating whether it was a target. Further details of the data acquisition can be found in Manoach et al (2003).…”

“…Regions known to be reliably activated by blocked versions of SIRP include the dorsolateral prefrontal cortex (DLPFC), intraparietal sulcus, lateral premotor cortex, supplementary motor area, and the insula (e.g., Manoach et al, 1997;Rypma and D'Esposito, 1999). This experiment was designed with the intent of investigating the neural circuitry underlying each epoch (encode, delay, probe) of the working memory task (Manoach et al, 2003).…”