Research reportEffects of prefrontal lesions on lexical processing and repetition priming: an ERP study
Introduction
Our general knowledge about the world, including facts, concepts, and word meanings, is often classified under the rubric of semantic memory. Semantic memory has been distinguished from episodic memory for personally experienced events and their respective contexts [85].1 The neuropsychological literature on semantic dementia and progressive aphasia implicates left temporal lobe regions in semantic memory 28, 87. Conversely, a number of neuroimaging studies point to left inferior prefrontal cortex (LIPC) as being crucial for retrieval from semantic memory 3, 7, 18, 33, 51, 52, 89, particularly retrieval of lexical knowledge, i.e., words and their meanings and their phonological forms 11, 36, 55. Based on results from positron emission tomography (PET) and functional magnetic resonance imaging (fMRI), a further division of labor within LIPC has been proposed by some investigators: the anterior portions of LIPC (areas 10, 47) are specifically involved in semantic processing, while activations in posterior LIPC regions (area 44) are related to more general word retrieval mechanisms or to phonological processing 2, 11, 57, 59. Studies of patients with focal lesions in left prefrontal cortex have not addressed this hypothesis.
Another subdivision of human memory is the distinction between explicit memory systems, whose contents are accessible to conscious awareness, and indirect or implicit forms of memory that are independent of conscious recollection [86]. One type of implicit memory, known as priming, is the improved ability to identify a stimulus after subsequent presentation. For example, priming in the lexical decision task is measured by a decrease in reaction time (RT) following repeated exposure [65]. Until recently, the neuroanatomical substrates of priming have evaded researchers. One emerging view is that visual word priming is reliant on the integrity of extrastriate cortex. Patients with lesions of right inferior temporal–occipital (temp–occip) cortex showed impaired priming in word stem completion [46]and lexical decision [75]. Furthermore, a patient with a right occipital resection exhibited intact explicit memory but impaired perceptual identification and word stem completion priming [17]. Deficient visual word priming has also been observed in patients with damage to left inferior, medial temp–occip cortex and the syndrome of alexia without agraphia 4, 46, 81. Hence, the existing neuropsychological evidence suggests that visual word priming requires both left and right temp–occip areas.
The functional neuroimaging techniques of PET and fMRI have been applied to questions of implicit memory mechanisms in an effort to localize these operations in human subjects. An early PET experiment found decreased blood flow in right occipital cortex, centered in the region of the lingual gyrus, during word stem completion priming [74]. This result was interpreted to mean that sensory processing became more efficient with stimulus repetition, reflected both in behavioral priming and in blood flow decreases in right occipital cortex. Subsequent experiments observed blood flow reductions in bilateral temp–occip regions 3, 66. Imaging studies have thus provided converging evidence on the importance of extrastriate cortex for visual word priming. Recent fMRI studies, however, have implied a left frontal contribution to certain kinds of priming. Activity in LIPC was reduced when semantic decisions were made on repeated words relative to new words 7, 18, 89. Likewise, repetition priming in living/non-living and concrete/abstract tasks was diminished in some patients with left frontal lesions [76]. Conversely, frontal lesions had no effect on word stem completion [69]or conceptual priming [19], so the precise role of left prefrontal cortex in various priming tasks remains unclear. The comparison between priming effects (based purely on stimulus repetition) and practice effects (based on repeated task performance) is likely to be a critical one.
Our understanding of lexical–semantic processing and repetition priming can be enhanced by recording electrophysiological activity that is time-locked to the cognitive events of interest. Event-related potentials (ERPs) are the summed activity of synchronized post-synaptic potentials (PSPs) recorded on the scalp [27]. Because of their excellent temporal resolution, ERPs can illuminate the temporal dynamics of the neural activity underlying lexical access, semantic integration, and repetition effects. Of particular interest are two ERP components, the N400 and the late positive component (LPC). The N400 is a negative-going potential, typically peaking at 400 ms post-stimulus, that is related to semantic processing [39]. The amplitude of the N400 is modulated by the extent to which a word is related to its prior context (see Ref. [40]for review), making it sensitive to both repetition priming and semantic priming. The LPC, a relative of the P300 component that peaks at about 600 ms, can be recorded during the repetition of words in lists [43].
Incidentally repeated or previously studied words elicit greater positivity than new words, beginning at 300 ms poststimulus and typically lasting for several hundred milliseconds 25, 34, 60, 88. This ERP word repetition effect (or `old/new effect') encompasses a decrease in N400 and an increase in LPC amplitude. A number of researchers have claimed that the ERP repetition effect is more closely related to episodic memory than to implicit forms of memory retrieval. In recognition paradigms, remembered items associated with `conscious recollection' evoke larger positive shifts than items associated with only relative familiarity 50, 70, 91. On the other hand, evidence for the involvement of familiarity or implicit memory mechanisms is provided by Alzheimer's patients, who despite their prominent deficits in explicit memory, demonstrate significant ERP effects when word repetition is incidental to the task 14, 62. It seems plausible that the ERP repetition effect contains contributions from neural sources participating in both explicit and implicit aspects of word retrieval 1, 49, 75, 77; the relative contributions of each may vary based on task requirements, age, and the presence of brain damage. For example, the ERP repetition effect is intact in the elderly in indirect memory tasks 14, 26, 35, 61, 77but not direct memory tasks 61, 77.
The neural structures that generate N400 and LPC have not been fully delineated. In particular, most intracranial and lesion studies of the ERP repetition effect have been conducted using explicit memory paradigms. However, non-overlapping (as well as overlapping) populations of generators are likely recruited when repetition is incidental, rather than integral to the task. Left anterior temporal lobectomy (ATL, 32, 63, 71) or right ATL [63]reduces the repetition effect to old words during recognition. Comparable results for incidental word repetition have not been reported. Depth recordings in the medial temporal lobe (MTL) have revealed potentials resembling the scalp N400 and LPC components elicited in recognition memory, lexical decision, and picture naming tasks 58, 72. Intracranial recordings from the anterior MTL and inferior temporal surface suggested that a major N400 generator is in anterior fusiform and parahippocampal gyri 41, 47, but depth N400 and LPC potentials have also been recorded in hippocampus, rhinal cortex, superior and middle temporal gyri, lateral orbitofrontal cortex, and near Broca's area 20, 22, 23. If left prefrontal cortex is important for lexical–semantic processing, one might expect that damage to this region would have dire consequences for the N400 component in particular.
Recent reviews of the neuroimaging literature 2, 48have listed about 20 studies that relate hemodynamic changes in left prefrontal cortex to retrieval of information from semantic memory. One difficulty in defining the significance of these prefrontal activations is whether they comprise a circuit that is essential for task performance. Furthermore, the limited temporal resolution of PET prevents it from establishing the sequence of events underlying blood flow changes. Other limitations of the PET methodology as specifically applied to language processing include the assumptions inherent in using the hierarchical, subtractive paradigm (discussed in Refs. 5, 9, 54). Therefore, a converging approach that compares the results obtained with PET/fMRI, ERPs, and neuropsychology can be most informative.
The goals of this study were to clarify: (1) the role of left inferior prefrontal cortex in lexical processing, (2) the necessity of lateral prefrontal cortex for intact behavioral and ERP correlates of repetition priming, and (3) whether prefrontal cortex makes differential contributions to the ERP repetition effect in implicit and explicit memory paradigms. A parallel study demonstrated that lateral prefrontal cortex was not critical for the ERP repetition effect in a recognition memory task [79]. To achieve the objectives stated above, the current experiment recorded ERPs from patients with focal frontal lesions to determine the importance of prefrontal cortex for verbal priming during lexical decision and for the generation of cognitive ERP components in this task.
Section snippets
Subjects
Subjects were 11 patients with focal brain lesions caused by strokes (mean age of 58.4 years, range 26–77) and 11 age-matched controls (mean 60.5 years, range 25–83). Patients were selected based on unilateral frontal lesion visible on CT or MRI scans and due to infarction in the precentral branch of the middle cerebral artery. Lesions were centered in the posterior portion of Brodmann areas 9 and 46, but damage extended inferiorly and posteriorly to areas 6, 8, 44, 45, and the temporal tip in
Behavioral performance
The ANOVA for RT data yielded significant main effects of stimulus type [F(1,20)=26.62, p<0.0001], condition [F(3,60)=103.47, p<0.0001], and group [F(1,20)=7.21, p<0.05]. Patients with frontal lesions were slower than controls, but all participants were faster for words than non-words and for repeated items at all lags compared to new stimuli. An interaction between stimulus type and lag was also observed [F(3,60)=6.39, p<0.005], suggesting greater RT priming for words than non-words. There
Discussion
Behavioral and ERP data from patients with focal lesions in lateral prefrontal cortex revealed the following: (1) the posterior frontal group, whose lesions included more extensive involvement of Broca's area and the insula, was significantly impaired on the lexical decision task, having both slower RTs and lower accuracy; (2) behavioral priming, as measured by a facilitation in RT, was not affected by either anterior or posterior frontal damage; (3) the ERP repetition effect, conversely, was
Acknowledgements
This work was supported by DC03023 from NIDCD and by NS21135 and PO NS17778 from NINDS. Many thanks to Bob Knight for his support and neurological expertise and to Marta Kutas and Anders Dale for providing their eyeblink correction algorithm.
References (94)
- et al.
Visual repetition priming for words relies on access to the visual input lexicon: evidence from a dyslexic patient
Neuropsychologia
(1994) - et al.
Topography of the N400: brain electrical activity reflecting semantic expectancy
Electroencephalogr. Clin. Neurophysiol.
(1993) - et al.
A PET study of word finding
Neuropsychologia
(1991) - et al.
Spatio-temporal stages in face and word processing: 1. Depth-recorded potentials in the human occipital, temporal, and parietal lobes
J. Physiol. (Paris)
(1994) - et al.
Spatio-temporal stages in face and word processing: 2. Depth-recorded potentials in the human frontal and Rolandic cortices
J. Physiol. (Paris)
(1994) - et al.
Source memory impairment in patients with frontal lobe lesions
Neuropsychologia
(1989) - et al.
Cognitive subtractions may not add up: the interaction between semantic processing and response mode
NeuroImage
(1997) - et al.
Luminance and spatial attention effects on early visual processing
Cogn. Brain Res.
(1995) - et al.
Event-related potentials and repetition priming in young, middle-aged and elderly normal subjects
Cogn. Brain Res.
(1993) Decreased response to novel stimuli after prefrontal lesions in man
Electroencephalogr. Clin. Neurophysiol.
(1984)
Scalp distributions of event-related potentials: an ambiguity associated with analysis of variance models
Electroencephalogr. Clin. Neurophysiol.
Event-related brain potentials during initial encoding and recognition memory of congruous and incongruous words
J. Mem. Lang.
Impaired word-stem priming in patients with temporal–occipital lesions
Neuropsychologia
A critical review of PET studies of phonological processing
Brain Lang.
Word repetition effects on event-related potentials in healthy young and old subjects, and in patients with Alzheimer-type dementia
Neuropsychologia
Priming and the brain
Neuron
Intact implicit memory in patients with frontal lobe lesions
Neuropsychologia
Human medial temporal lobe potentials evoked in memory and language tasks
Electroencephalogr. Clin. Neurophysiol.
Is prefrontal cortex involved in cued recall? A neuropsychological test of PET findings
Neuropsychologia
Recognition memory with and without retrieval of context: an event-related potential study
Neuropsychologia
Memory with and without awareness: performance and electrophysiological evidence of savings
J. Exp. Psychol.: Learn. Mem. Cogn.
Beyond HERA: contributions of specific prefrontal brain areas to long-term memory retrieval
Psychonom. Bull. Rev.
Functional anatomical studies of explicit and implicit memory retrieval tasks
J. Neurosci.
PET activation and language
Clin. Neurosci.
Semantic encoding and retrieval in the left inferior prefrontal cortex: a functional MRI study of task difficulty and process specificity
J. Neurosci.
The anatomy of phonological and semantic processing in normal subjects
Brain
Language functions explored in normal subjects by positron emission tomography: a critical review
Hum. Brain Mapp.
Neural mechanisms for visual memory and their role in attention
Proc. Natl. Acad. Sci. U.S.A.
Phonology, semantics, and the role of the left inferior prefrontal cortex
Hum. Brain Mapp.
PET studies of auditory and phonological processing: effects of stimulus characteristics and task demands
J. Cogn. Neurosci.
Event-related potentials (ERPs) during repetition priming in Alzheimer's patients and young and older controls
J. Clin. Exp. Neuropsychol.
Regional cerebral activity associated with the incidental processing of pseudo-words
Hum. Brain Mapp.
Double dissociation between memory systems underlying explicit and implicit memory in the human brain
Psychol. Sci.
Functional magnetic resonance imaging of semantic memory processes in the frontal lobes
Psychol. Sci.
Implicit and explicit conceptual memory following frontal lobe damage
J. Cogn. Neurosci.
Intracranial topography of event-related potentials (N400/P600) elicited during a continuous recognition memory task
Psychophysiology
Sources of attention-sensitive visual event-related potentials
Brain Topogr.
Intracranial potentials evoked by words and pseudowords during reading and lexical decision
Soc. Neurosci. Abstr.
Cognitive evoked potentials as modulatory processes in human memory formation and retrieval
Hum. Neurobiol.
Event-related potential correlates of repetition priming and stimulus classification in young, middle-aged, and older adults
J. Gerontol.: Psychol. Sci.
Semantic dementia: progressive fluent aphasia with temporal lobe atrophy
Brain
Neuroanatomical correlates of encoding in episodic memory: levels of processing effect
Proc. Natl. Acad. Sci. U.S.A.
Effects of inter-item lag on word repetition: an event-related potential study
Psychophysiology
The neural substrates underlying word generation: a bilingual functional-imaging study
Proc. Natl. Acad. Sci. U.S.A.
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2022, NeuropsychologiaCitation Excerpt :The convergent evidence from neuropsychology provided here helps to bolster the conclusion that left lateral frontal cortex is indeed necessary for intact priming (see also Martin and Gotts, 2005, for discussion). Swick (1998) studied repetition priming in lexical decision with 11 frontal patients with damage due to stroke but failed to find an impairment in repetition priming. The delays used in this study were much shorter (60 s or less) than those used in the current study, and the patient lesions were concentrated ventrally to the inferior frontal junction.
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2021, Brain and LanguageEvent-related potentials in an associative word pair learning paradigm
2021, Journal of NeurolinguisticsLeft middle temporal and inferior frontal regions contribute to speed of lexical decision: A TMS study
2015, Brain and CognitionCitation Excerpt :Whereas some neuroimaging studies of word reading or lexical decision have reported activation of these regions (Bookheimer, Zeffiro, Blaxton, Gaillard, & Theodore, 1995; Fiez & Petersen, 1998; Heim et al., 2009; Madden et al., 2002), others have not (Gold, Andersen, Jicha, & Smith, 2009; Petersen et al., 1988). In addition, although large peri-Sylvian lesions tend to impair word recognition performance (Dronkers, Wilkins, Van Valin, Redfern, & Jaeger, 2004; Hagoort, 1993; Milberg & Blumstein, 1981; Swick, 1998), such lesions typically extend beyond the aLIFG or LMTG. For instance, a lack of priming related to ambiguous words has been observed in patients with lesions of left prefrontal cortex (Metzler, 2001).
Explicit and implicit memory in female college students with schizotypal traits: An event-related potential study
2011, Biological PsychologyCitation Excerpt :Numerous studies have shown that the ERPs elicited by repeated items (old) are generally more positive-going than those elicited by items presented for the first time (new): this has been referred to as the old/new effect or the repetition effect. The old/new effect, which has been observed in both explicit and implicit memory tasks (Boehm et al., 2005; Friedman et al., 1992; Swick, 1998), usually begins at about 250–300 ms and lasts about 700–800 ms after stimulus onset (Kayser et al., 2010). A number of studies have used ERPs to investigate the explicit verbal memory of schizophrenic patients and have reported a reduced old/new effect (i.e., reduced difference-amplitudes between new and old stimuli) in this population (Baving et al., 2000; Kayser et al., 2009; Tendolkar et al., 2002).