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[Abstract Title]. - Society for Neuroscience

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NIH MH064498<br />

<strong>Title</strong>: A TMS “ping” during fMRI reveals physiological consequences of functional connectivity<br />

and dissociates multivariate from univariate maps of working memory storage<br />

Authors: *E. FEREDOES 1 , A. HELLER 2 , G. TONONI 3 , T. S. WOODWARD 1 , B. R.<br />

POSTLE 2,3 ;<br />

1 Psychiatry, Univ. of British Columbia, Vancouver, BC, Canada; 2 Psychology, 3 Psychiatry,<br />

Univ. of Wisconsin-Madison, Madison, WI<br />

<strong>Abstract</strong>: It is widely accepted that multivariate approaches to fMRI data analysis can, by<br />

measuring functional connectivity, provide in<strong>for</strong>mation about distributed functional networks<br />

that cannot be inferred from traditional “massively univariate” analyses. However, most<br />

multivariate methods are nonetheless subject to the same inferential constraints fundamental to<br />

all correlational methods (i.e., neither necessity nor causality can be inferred). We used<br />

transcranial magnetic stimulation (TMS) to evaluate causally a verbal storage network suggested<br />

by a constrained principal components analysis (cPCA) of working memory data. The logic was<br />

that a physiological consequence of functional connectivity should be reflected in the manner in<br />

which a TMS-triggered impulse propagates through the putative functional network. (An analogy<br />

is to “ping” a network of computers by sending a signal from one computer to determine which<br />

other computers are actively connected to the network). In scanning session 1, subjects<br />

per<strong>for</strong>med short-term delayed recognition (DR) of letters at two loads: 2 or 5 items. cPCA<br />

identified a (functionally connected) network of voxels whose delay-period activity was sensitive<br />

to variation of load (an operationalization of “short-term storage”). Scanning session 2 featured a<br />

2 (TMS present; TMS absent) x 3 (Letter DR; Location DR; no task) factorial design. A single<br />

pulse of TMS was delivered in the middle of the delay period to either a node in the cPCAdefined<br />

load-sensitive network, or to a control area. The cPCA map from session 1 was<br />

coregistered into session 2 space and within it the TMS “ping” increased Letter delay-period<br />

activity (i.e., Letter-DR/TMS-present > Letter-DR/TMS-absent), whereas it decreased Location<br />

delay-period activity. Univariate delay-activity maps were also created <strong>for</strong> Letter-DR/TMSabsent<br />

and Location-DR/TMS-absent trials. Within these univariate masks, TMS had the<br />

uni<strong>for</strong>m effect of decreasing delay-period activity. Notably, within the left and right dorsolateral<br />

prefrontal cortex foci identified by the GLM <strong>for</strong> Letter-DR/TMS-absent trials, delay-period<br />

activity was greater during Letter-DR/TMS-absent than Letter-DR/TMS-present trials. These<br />

results suggest that a physiological consequence of functional connectivity is facilitation of<br />

synaptic transmission between nodes in the network. They also provide a stark demonstration<br />

that delay-period activity revealed by univariate analyses cannot be assumed a priori to<br />

correspond to the short-term storage of in<strong>for</strong>mation.<br />

Disclosures: E. Feredoes , None; T.S. Woodward, None; G. Tononi, None; B.R. Postle,<br />

None; A. Heller, None.<br />

Poster

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