Functional differentiation of medial temporal and frontal regions involved in processing novel and familiar words: an fMRI study

Abstract

Results of recent functional magnetic resonance imaging (fMRI) studies of memory are not entirely consistent with lesion studies. Furthermore, although imaging probes have identified neural systems associated with processing novel visual episodic information, auditory verbal memory using a novel/familiar paradigm has not yet been examined. To address this gap, fMRI was used to compare the haemodynamic response when listening to recently learned and novel words. Sixteen healthy adults (6 male, 10 female) learned a 10-item word list to 100% criterion, approximately 1 h before functional scanning. During echo-planar imaging, subjects passively listened to a string of words presented at 6-s intervals. Previously learned words were interspersed pseudo-randomly between novel words. Mean scans corresponding to each word type were analysed with a random-effects model using statistical parametric mapping (SPM96). Familiar (learned) words activated the right prefrontal cortex, posterior left parahippocampal gyrus, left medial parietal cortex and right superior temporal gyrus. Novel words activated the anterior left hippocampal region. The results for the familiar words were similar to those found in other functional imaging studies of recognition and retrieval and implicate the right dorsolateral prefrontal and left posterior medial temporal lobe (MTL) regions. The results for novel words require replication, but are consistent with the substantial lesion and PET literature implicating the anterior MTL as a critical site for processing novel episodic information, presumably to permit encoding. Together, these results provide evidence for an anterior-posterior functional differentiation within the MTL in processing novel and familiar verbal information. The differentiation of MTL functions that was obtained is consistent with a large body of PET activation studies but is unique among fMRI studies, which to date have differed from results with PET. Further, the finding of left MTL lateralization is consistent with lesion-based material-specific models of memory.

Selection of Currently Relevant Memories by the Human Posterior Medial Orbitofrontal Cortex

“…In agreement with earlier functional imaging studies demonstrating activation of the medial temporal lobe (hippocampus, parahippocampal gyrus, or both) in tasks of new learning (Stern et al, 1996;Tulving et al, 1996;Dolan and Fletcher, 1997;Gabrieli et al, 1997;Saykin et al, 1999;Strange et al, 1999), we found medial temporal activation only when subjects encountered the picture series for the first time. This finding agrees with our clinical data showing that patients who fail only in the new learning part of a continuous recognition task (first run) typically have medial temporal damage (Schnider et al, 1996c;Schnider and Ptak, 1999) and with a wealth of clinical studies demonstrating the importance of the medial temporal lobe for new learning (Scoville and Milner, 1957;Victor et al, 1961;DeJong et al, 1969;Zola-Morgan et al, 1986;Squire, 1992;Schnider et al, 1994;Mishkin et al, 1997;Nadel and Moscovitch, 1997).…”

Memory encoding and hippocampally-based novelty/familiarity discrimination networks

“…Regional cerebral blood flow (rCBF), measured during a yes/no recognition memory test, was higher for novel than for familiar items at a number of sites in the extended limbic system. Other research has corroborated the general thrust of these early findings [7,9,15,17,18], and has extended the novelty assessment networks to other cerebral regions beyond the limbic system, including a number of anterior and posterior neocortical sites [11,12,19]. We proposed a specific relation between novelty assessment and memory encoding in the form of a novelty encoding hypothesis.…”

“…As mentioned earlier, we selected the seed voxels for our analysis in the hippocampus because of considerable evidence in the literature about the involvement of the hippocampus in novelty detection [1,2,[5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]47]. It is also generally accepted that novelty detection involves regions beyond the hippocampus [ 1,2,12,17,19,20].…”

“…Typically, this voxel is chosen based on previous analyses of the data, theoretical motivation, or both. In the present case, we targeted the hippocampus proper for the selection of the seed voxel because previous research has demonstrated the involvement of the hippocampus in novelty assessment [7,11,12,[17][18][19][20]. Because of the size of the hippocampal region and evidence for its functional heterogeneity [17,35,36], however, the selection of a single representative voxel (a single coordinate in Talairach space) can be difficult.…”

“…Novelty/familiarity discrimination (also known as novelty detection, or novelty assessment) is useful for the organism in a variety of situations, can take a number of specific forms, and can serve several functions (see reviews by [1][2][3][4]). The hippocampal system has been found to be critically involved in many tasks involving neural novelty/familiarity (henceforth just 'novelty') discrimination [1,2,[5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. In this report, we describe a positron emission tomography (PET) study whose purpose was to explore the idea that novelty discrimination does not depend on the hippocampal system alone but is subserved by large-scale neuronal networks which include but go beyond the hippocampal system.…”