Elsevier

NeuroImage

Volume 49, Issue 1, 1 January 2010, Pages 1099-1107
NeuroImage

Neural systems supporting lexical search guided by letter and semantic category cues: A self-paced overt response fMRI study of verbal fluency

https://doi.org/10.1016/j.neuroimage.2009.07.036Get rights and content

Abstract

Verbal fluency tasks have been widely used to evaluate language and executive control processes in the human brain. FMRI studies of verbal fluency, however, have used either silent word generation (which provides no behavioral measure) or cued generation of single words in order to contend with speech-related motion artifacts. In this study, we use a recently developed paradigm design to investigate the neural correlates of verbal fluency during overt, free recall, word generation so that performance and brain activity could be evaluated under conditions that more closely mirror standard behavioral test demands. We investigated verbal fluency to both letter and category cues in order to evaluate differential involvement of specific frontal and temporal lobe sites as a function of retrieval cue type, as suggested by previous neuropsychological and neuroimaging investigations. In addition, we incorporated both a task switching manipulation and an automatic speech condition in order to modulate the demand placed on executive functions. We found greater activation in the left hemisphere during category and letter fluency tasks, and greater right hemisphere activation during automatic speech. We also found that letter and category fluency tasks were associated with differential involvement of specific regions of the frontal and temporal lobes. These findings provide converging evidence that letter and category fluency performance is dependent on partially distinct neural circuitry. They also provide strong evidence that verbal fluency can be successfully evaluated in the MR environment using overt, self-paced, responses.

Introduction

Neuropsychological investigations have shown that verbal fluency, as measured by the ability to generate lists of words aloud under time constraint, relies on the coordinated activity of a number of brain areas, particularly in the frontal and temporal lobes of the left hemisphere. Damage to the left frontal lobe, especially to left inferior frontal cortex (LIFC) has consistently been shown to impair verbal fluency, even in patients who are not overtly aphasic (e.g., Baldo and Shimamura, 1998, Milner, 1964, Thompson-Schill et al., 1998). In addition, there is evidence that the generation of word lists to letter cues (letter fluency, e.g., “tell me all the words you can think of that begin with the letter A”) relies on a partially different network of brain regions than the generation of word lists to semantic category cues (category fluency e.g., “tell me all the animals you can think of”). Studies have shown, for example, that frontal lobe damage results in disproportionate impairment to letter fluency (e.g. Hodges et al., 1999, Miller, 1984, Baldo et al., 2001, Moscovitch, 1994), while temporal lobe damage impairs semantic category fluency to a greater extent than letter fluency (e.g. Hodges et al., 1999, Newcombe and Russel, 1969, Butters et al., 1986, Monsch et al., 1994, Chan et al., 1993, Baldo et al., 2006). Functional neuroimaging studies, using positron emission tomography (Mummery et al., 1996, Gourovitch et al., 2000) and fMRI (e.g., Perani et al., 2003a, Perani et al., 2003b) have generally supported these findings (for review, see Costafreda et al. (2006)).

Motivated by studies of patients with focal brain lesions, verbal fluency tasks have been used increasingly to evaluate language-related and executive control processes in a variety of non-focal disorders including traumatic brain injury (Henry and Crawford, 2004), depression (Wolfe et al., 1987), Alzheimer's disease (Monsch et al., 1992, Monsch et al., 1994), Huntington's disease (Monsch et al., 1994), schizophrenia (Saykin et al., 1991, Phillips et al., 2004), attention deficit/hyperactivity disorder (Geurts et al., 2004), and autism (Turner, 1999). It is therefore of considerable interest to elucidate the neural systems involved in performing these tasks using non-invasive methods.

The fluency paradigms used in nearly all fMRI studies, however, have differed markedly from the procedure used in neuropsychological investigations. Perhaps most important among these differences, the standard behavioral paradigm in neuropsychological studies requires free recall, with subjects producing words aloud as quickly as possible within a limited period of time. In contrast, in order to mitigate task-related motion artifacts, fMRI studies have typically required either covert word generation (e.g., Gurd et al., 2002, Hirshorn and Thompson-Schill, 2006, Perani et al., 2003a, Perani et al., 2003b), or overt, but experimenter-paced single word production (e.g., Phelps et al., 1997, Abrahams et al., 2003). Covert word generation lacks a behavioral correlate, and the results are therefore difficult to interpret and validate, particularly when studying patient groups. While providing the behavioral correlate, paced overt single word production tasks are also problematic. These procedures reduce cognitive demands relative to the behavioral task by allowing subjects more time to reflect upon their word choice, while increasing the need to inhibit responses (see Basho et al. (2007) and Abrahams et al. (2003) for discussions of these issues). Verbal fluency tasks are often used clinically because they provide measures of the efficiency of selecting and retrieving phonological/orthographic and semantic category information, and require efficient task initiation, planning, organization, and flexibility. These demands are likely to be markedly reduced or absent when responses are generated covertly or are artificially constrained by experimenter-determined pacing.

Fortunately, paradigms for allowing self-paced overt responses in fMRI while mitigating the artifacts from motion have recently been introduced. Basho et al. (2007), for example, investigated category fluency in an overt self-paced design. An overt speech baseline was included in an attempt to control for task-related motion artifacts (e.g., Barch et al., 1999). A potential difficulty with this design is that the main effect of speaking aloud cannot be investigated. This, in turn, may have contributed to the surprising finding that covert word generation lead to greater neural activity in a number of brain regions, relative to overt word generation. In contrast, no brain region showed more activity for the overt, relative to the covert task (>Basho et al., 2007). A different approach to reducing task-related motion artifacts is by using an event-related paradigm or a blocked design with relatively short (10 s) task and rest periods (Birn et al., 2004, Soltysik and Hyde, 2006). These paradigms have been shown to produce reliable measures of activation using relatively simple speech tasks (e.g., cued single word reading). However, their ability to distinguish differences in activation expected to result from variations in fluency task demands has not been investigated.

Our primary goal was to investigate the neural correlates of verbal fluency during overt, free recall, word generation so that performance and brain activity could be evaluated under conditions that more closely mirror standard behavioral test demands. While the 10 s of word generation required is relatively short compared to typical behavioral word generation tasks, and will therefore be easier to complete, it does require self-paced spontaneous generation of multiple words, a fundamental aspect of behavioral fluency tasks. Furthermore, the briefer word generation time will be important if this paradigm is to be used in the future with clinical groups that are impaired on behavioral word fluency tasks. It can be difficult to interpret functional imaging findings on tasks for which behavior is not equated. It is our clinical observation in both Alzheimer's disease (AM) and Autism Spectrum Disorders (LK) that the initial 10 s of response is similar to typical controls, whereas later in the course of 1 min, word production drops off. Therefore, it is hoped that a briefer interval of self-paced word generation will tap fundamental processes associated with verbal fluency while allowing equivalent word output in typical and clinical groups. In contrast to previous studies of overt self-paced verbal fluency, our paradigm included both letter and category cues to evaluate differential involvement of specific frontal and temporal lobe sites as a function of retrieval cue type, as suggested by previous neuropsychological and neuroimaging investigations. We also incorporated a switching manipulation that required subjects to alternate retrieval according to two cues (two letters, two categories), in order to place greater emphasis on executive control processes typically linked to frontal lobe functioning (Baddeley et al., 2001). Switching fluency tasks have been commonly used to evaluate cognitive flexibility in a variety of clinical populations including schizophrenia (Gourovitch et al., 1996), Parkinson's disease (Gurd and Oliveira 1996), Alzheimer's disease (Houston et al., 2005), obsessive compulsive disorders (Martin et al., 1993), and HIV-associated cognitive deficits (Iudicello et al., 2008). Finally, we included an automatic speech condition that required subjects to produce a highly over-learned sequence of words to provide a language production baseline and to control for language output effects.

The neural substrate for automatic speech is of interest in its own right. In the late 1800s, Hughlings Jackson suggested that nonpropositional, automatic speech may be under right hemisphere control (Jackson, 1879). This idea has received some support from lesion studies showing that speech automatisms (e.g., over-learned phrases, curse words) often occur in patients with left hemisphere brain damage and aphasia, whereas, relative to patients with left-sided lesions, patients with right hemisphere damage are impaired in producing automatic speech (for review see Code (1997)).

We had a number of predictions based on previous neuropsychological and neuroimaging findings. First, we expected that, relative to automatic speech, the neural network associated with word generation during the fluency tasks (i.e., in response to specific letter and semantic category cues) would be strongly lateralized to the left hemisphere, even though it would be expected that many more words would be produced under the automatic than the other word generation conditions. Conversely, we expected that automatic speech would show more extensive right hemisphere activity. We also expected that both the letter and semantic tasks would be associated with activity in a number of brain regions, prominently including LIFC (reflecting selection and retrieval demands) and left posterior temporal cortices (reflecting the site of stored information being retrieved). Moreover, we expected letter fluency to yield greater LIFC involvement than category fluency due to increased selection demands associated with retrieving words based on spelling rules (words beginning with a specific letter) relative to word retrieval based on a semantic category (words denoting objects belonging to a single, common category). In contrast, the category tasks would be expected to produce more posterior temporal lobe activity as a reflection of conceptually-driven word retrieval demands that define these, but not letter fluency tasks (e.g., Martin et al., 1994). Finally, relative to the single cue conditions, the two cue switching conditions should also produce increased LIFC (Sohn et al., 2000) and/or posterior parietal (Gurd et al., 2002, Gurd et al., 2003) activity because of the greater demands these tasks place on controlled retrieval processes.

Section snippets

Subject and imaging parameters

Fourteen, right-handed, healthy volunteers participated in the study (7 female; mean age = 32.2 years, range 22–48). All subjects spoke English as their first language, had normal or corrected-to-normal visual acuity, and no known history of neurological impairments or reading/vocabulary difficulties. Informed consent was obtained in writing under an approved National Institute of Mental Health protocol. All participants were financially compensated for their participation according to NIH

Behavior

As expected, subjects generated more words during the automatic speech condition (“months”) (mean ± std. error of the mean: 12.0 ± 1.4 words) than during any of the other fluency conditions (all p's  < 0.0001; 1 letter: 5.0 ± 0.4 words, 1 category: 6.0 ± 0.5 words, 2 letters: 5.2 ± 0.4 words, 2 categories: 4.9 ± 0.3 words). The number of words produced during the different fluency tasks, however, did not differ significantly (all p's > 0.10).

Imaging

Relative to the 10 s rest periods, word generation during the fluency

Discussion

This study provides strong evidence that different types of verbal fluency tasks can be successfully performed and evaluated in the MR environment using overt responses that are self-paced. Although the feasibility of the paradigm used in this study has been demonstrated before (Birn et al., 2004), the prior study used a task that was highly constrained — reading aloud single words. The current study is the first to show that this paradigm can be successfully used to evaluate overt free recall.

Conclusions

In this study we were able to measure brain activity when subjects generated aloud lists of words to specific retrieval cues, thereby more closely mirroring standard behavioral test demands for unpaced word generation than in previous fMRI investigations. Consistent with previous findings, we found that letter and category fluency tasks were associated with differential involvement of frontal and temporal lobes — with a greater activation in left pre-central and inferior frontal gyrus for

Acknowledgments

This research was supported by the Intramural Research Program of the National Institute of Mental Health.

References (54)

  • HirshornE.A. et al.

    Role of the left inferior frontal gyrus in covert word retrieval: neural correlates of switching during verbal fluency

    Neuropsychologia

    (2006)
  • HutchinsonM. et al.

    Task-specific deactivation patterns in functional magnetic resonance imaging

    Magn. Reson. Imaging

    (1999)
  • MartinA. et al.

    Lack of evidence for Huntington's disease-like cognitive dysfunction in obsessive–compulsive disorder

    Biol. Psychiatry

    (1993)
  • MartinA. et al.

    Word retrieval to letter and semantic cues: a double dissociation in normal subjects using interference tasks

    Neuropsychologia

    (1994)
  • McCandlissB.D. et al.

    The visual word form area: expertise for reading in the fusiform gyrus

    Trends Cogn. Sci.

    (2003)
  • PeraniD. et al.

    A fMRI study of word retrieval in aphasia

    Brain Lang.

    (2003)
  • PhillipsT.J. et al.

    Semantic fluency is impaired but phonemic and design fluency are preserved in early-onset schizophrenia

    Schizophr. Res.

    (2004)
  • SchacterD.L. et al.

    Reductions in cortical activity during priming

    Curr. Opin. Neurobiol.

    (2007)
  • SoltysikD.A. et al.

    Strategies for block-design fMRI experiments during task-related motion of structures of the oral cavity

    NeuroImage

    (2006)
  • WolfeJ. et al.

    Verbal memory deficits associated with major affective disorders: a comparison of unipolar and bipolar patients

    J. Affect. Disord.

    (1987)
  • AbrahamsS. et al.

    Functional magnetic resonance imaging of verbal fluency and confrontation naming using compressed image acquisition to permit overt responses

    Hum. Brain Mapp.

    (2003)
  • BaddeleyA. et al.

    Working memory and the control of action: evidence from task switching

    J. Exp. Psychol. Gen.

    (2001)
  • BaldoJ.V. et al.

    Letter and category fluency in patients with frontal lobe lesions

    Neuropsychology

    (1998)
  • BaldoJ.V. et al.

    Verbal and design fluency in patients with frontal lobe lesions

    J. Int. Neuropsychol. Soc.

    (2001)
  • BaldoJ.V. et al.

    Role of frontal versus temporal cortex in verbal fluency as revealed by voxel-based lesion symptom mapping

    J. Int. Neuropsychol. Soc.

    (2006)
  • BirnR.M. et al.

    Magnetic field changes in the human brain due to swallowing or speaking

    Magn. Reson. Med.

    (1998)
  • ChanA.S. et al.

    An assessment of the semantic network in patients with Alzheimer's disease

    J. Cogn. Neurosci.

    (1993)
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