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

Letter and category fluency tasks involved different specific regions of the frontal and temporal lobes.

“We also found that letter and category fluency tasks were associated with differential involvement of specific regions of the frontal and temporal lobes.”

Compared with category fluency, letter fluency increased activity in left inferior frontal gyrus, bilateral superior parietal cortex, and bilateral ventral occipitotemporal cortex around the occipital temporal sulcus.

“Relative to category fluency, letter fluency yielded greater activity in the left inferior frontal gyrus, bilateral superior parietal cortex, and in the bilateral ventral occipitotemporal cortex centered on the occipital temporal sulcus.”

During automatic speech, bilateral superior temporal and precentral gyri showed greater activity than during controlled retrieval.

“Consistent with this increased output, a number of brain regions - including the superior temporal and precentral gyri, bilaterally - showed enhanced activity during this automatic speech condition relative to the controlled retrieval conditions.”

Participants generated more words when reciting the months in chronological order than when retrieving words to letter or category cues.

“As expected, subjects produced significantly more words when repeatedly reciting the months of the year in chronological order than when retrieving words to specific letter and category cues.”

Switching between two categories or two letters increased activation in several regions, including left middle frontal gyrus, left superior parietal cortex, left fusiform, and precuneus.

“The additional task demand of switching between two categories or two letters resulted in greater activation in a number of these regions including the left middle frontal gyrus, left superior parietal cortex, left fusiform, and the precuneus (Figure 3 and Table 1).”

Compared with rest, fluency word generation caused strong bilateral activation across frontal, parietal, and occipitotemporal cortex and the anterior cingulate.

“Relative to the 10 s rest periods, word generation during the fluency tasks produced robust and widespread bilateral activation of frontal, parietal, and occipitotemporal cortices, and the anterior cingulate.”

Subjects generated more words during the automatic speech condition than during any of the other fluency conditions.

“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).”

Compared with category and letter fluency, reciting months in order increased activity in bilateral precentral gyrus, precuneus, left superior temporal gyrus, and a larger right hemisphere area spanning right superior temporal and supramarginal gyri.

“Specifically, relative to the category and letter fluency tasks, repeated retrieval of the names of the months of the year in chronological order yielded increased activity in bilateral precentral gyrus (motor and premotor cortices), precuneus, left superior temporal gyrus, and a more extensive region of activation in the right hemisphere covering both right superior temporal gyrus and right sup”

• AssumptionRests on an assumption: Naming months serves as a valid baseline for language production and controls for output effects.

Compared with automatic speech, fluency tasks strongly activated wide areas of left ventral occipitotemporal cortex including fusiform gyrus, left parietal and frontal cortex, the supplemental motor area, and bilateral thalamus extending into left caudate.

“In contrast, relative to automatic speech, the fluency conditions elicited robust activity in broad expanses of left ventral occipitotemporal cortex, including fusiform gyrus, (Fig 1b) left parietal and left frontal cortices (Fig 1c), as well as the supplemental motor area (SMA), and bilateral thalamus extending into the left caudate (Fig. 1c, Table 1).”

• AssumptionRests on an assumption: Naming months serves as a valid baseline for language production and controls for output effects.

The number of words produced during the different fluency tasks did not differ significantly.

“The number of words produced during the different fluency tasks, however, did not differ significantly (all p’s > .10).”

Other activated regions, including posterior temporal-parietal cortex centered on the supramarginal gyrus, were right-lateralized.

“Moreover, other activated regions, including a large region of posterior temporal-parietal cortex centered on the supramarginal gyrus, were lateralized to the right hemisphere.”

The superior temporal and precentral activations were more extensive in the right than the left hemisphere.

“An interesting aspect of the activations in both of these sites is that they were considerably more extensive in the right than left hemisphere (see Table 1).”

In some regions, automatic speech produced almost no detectable BOLD response versus rest, while fluency tasks produced robust responses.

“In fact, in some of these regions, automatic speech resulted in almost no detectable BOLD response compared to rest, whereas the fluency tasks produced robust responses, consistent with claims that these left hemisphere sites are involved in strategic lexical and semantic search and retrieval processes (see Fig 1).”

Letter fluency showed greater left premotor/inferior frontal gyrus responses than category fluency.

“In the left hemisphere, letter fluency was associated with enhanced responses in the left premotor/inferior frontal gyrus, relative to the category fluency tasks.”

Letter fluency produced greater activity than category fluency in discrete bilateral occipitotemporal cortex regions centered on the occipital temporal sulcus.

“Specifically, letter fluency was found to show greater activity than category fluency in relatively discrete bilateral regions of the occipitotemporal cortex centered on the occipital temporal sulcus.”

Category fluency showed greater left fusiform and left middle frontal gyrus activity than letter fluency.

“In contrast, category fluency showed enhanced activity in the left fusiform and left middle frontal gyrus.”

Switching between two letters or two categories increased bilateral posterior parietal activation.

“In addition, increased activation was observed in bilateral posterior parietal regions, a finding consistent with previous reports using covert verbal fluency tasks (Gurd et al., 2002; Gurd et al., 2003).”

Viewing whole words activated primary visual cortex bilaterally more than viewing single letters.

“In fact, viewing whole words activated primary visual cortex, bilaterally, to a greater extent relative to viewing single letters (see Fig 2).”

Both semantic and phonemic fluency tasks produced greater activation than the over-learned category control in left frontal, posterior ventral temporal, and superior parietal cortices.

“Both the semantic and phonemic fluency tasks produced greater activation in the left frontal, posterior ventral temporal, and superior parietal cortices, compared to the over-learned category control condition.”

Coordinated activity across multiple brain regions, particularly left frontal and temporal areas, underlies verbal fluency.

“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.”

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The neural circuits supporting letter and category fluency are partly separate.

“These findings provide converging evidence that letter and category fluency performance is dependent on partially distinct neural circuitry.”

Overt, self-paced responses allow successful assessment of verbal fluency inside the MR scanner.

“They also provide strong evidence that verbal fluency can be successfully evaluated in the MR environment using overt, self-paced, responses.”

• AssumptionRests on an assumption: Naming months serves as a valid baseline for language production and controls for output effects.

Bilateral precentral gyrus activation likely reflected overt articulation.

“Bilateral activation of the precentral gyrus was also observed, likely reflecting overt speech production (articulation).”

Temporal lobe damage impairs semantic category fluency more than letter fluency.

“while temporal lobe damage impairs semantic category fluency to a greater extent than letter fluency (e.g. Hodges et al. 1999; Newcombe, 1969, Butters et al.; 1987; Monsch, 1994; Chan et al; 1993; Baldo et al., 2006).”

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Frontal lobe damage disproportionately impairs letter fluency.

“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 et al., 1994)”

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The study strongly indicates that various verbal fluency tasks can be performed and assessed successfully in the MR scanner with overt, self-paced responses.

“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.”

• AssumptionRests on an assumption: Naming months serves as a valid baseline for language production and controls for output effects.

New paradigms have recently been introduced that permit self-paced overt responses in fMRI while reducing motion artifacts.

“Fortunately, paradigms for allowing self-paced overt responses in fMRI while mitigating the artifacts from motion have recently been introduced.”

Most fMRI fluency paradigms differ substantially from the procedures used in neuropsychological testing.

“The fluency paradigms used in nearly all fMRI studies, however, have differed markedly from the procedure used in neuropsychological investigations.”

Such designs have yielded reliable activation measures for fairly simple speech tasks.

“These paradigms have been shown to produce reliable measures of activation using relatively simple speech tasks (e.g., cued single word reading).”

In some areas, such as orbitofrontal cortex, the time course showed both motion-artifact features and a slower return to baseline during rest, suggesting a mix of motion-induced changes and task-related neural activity.

“In some brain regions, such as the orbitofrontal cortex, the signal intensity time course not only showed features consistent with task-related motion artifact, but also showed a slower return to baseline during the rest period, indicating that this region could contain a combination of motion-induced signal changes and task-related neuronal activity.”

Repeated retrieval of an over-learned word sequence produced greater right hemisphere activity than effortful generation of unique words.

“Thus, repeated retrieval of the same highly over-learned sequence of words led to enhanced right hemisphere activity relative to considerably more effortful tasks requiring the generation of a unique list of words on every trial.”

The brain network for letter-cued word generation is partly distinct from that for semantic category-cued generation.

“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”).”

The prior study (Birn et al., 2004) used a highly constrained task of reading aloud single words.

“Although the feasibility of the paradigm used in this study as been demonstrated before (Birn et al., 2004), the prior study used a task that was highly constrained – reading aloud single words.”

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The right-hemisphere enhancement is noteworthy because it contrasts with the usual repetition suppression seen when stimuli and tasks are repeated.

“This finding is particularly noteworthy given the extensive literature showing that neural activity typically decreases when stimuli and tasks are repeated (i.e., repetition suppression; Grill-Spector et al., 2006; Schacter et al., 2007).”

This is the first study to examine overt, unpaced verbal fluency across multiple retrieval conditions.

“In addition, although there have been a few previous reports on overt fluency; the current study is the first to investigate overt, unpaced verbal fluency under multiple retrieval conditions.”

One possible problem with the Basho et al. design is that it cannot examine the main effect of speaking aloud.

“A potential difficulty with this design is that the main effect of speaking aloud cannot be investigated.”

To reduce motion artifacts, fMRI studies usually ask for either silent word generation or single words spoken at a pace set by the experimenter.

“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 & Thompson-Schill, 2006; Perani et al., 2003), or overt, but experimenter-paced single word production (e.g., Phelps et al., 1997; Abrahams et al., 2003).”

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Left frontal damage, especially in left inferior frontal cortex, disrupts verbal fluency in patients who are not overtly aphasic.

“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 & Shimamura, 1998; Milner, 1964; Thompson-Schill et al., 1998).”

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This is the first study to demonstrate that the paradigm can successfully assess overt free recall.

“The current study is the first to show that this paradigm can be successfully used to evaluate overt free recall.”

Silent word generation provides no behavioral measure, so its results are hard to interpret and validate, especially in patients.

“Covert word generation lacks a behavioral correlate, and the results are therefore difficult to interpret and validate, particularly when studying patient groups.”

Because the motion artifact hinders precise estimation of activation amplitude, this region was excluded from the reported results.

“The presence of the motion artifact, however, makes a precise estimation of the activation amplitude more difficult, and as a result this region was not included in the above described results.”

This null result is consistent with previous studies.

“Surprising, but again consistent with previous studies (Gurd et al., 2002; Gurd et al., 2003), no enhanced activity was found in the more anterior frontal region (the middle frontal gyrus) found to be more active for category compared to letter fluency.”

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There is a possibility of missing activation or misestimating response amplitude when BOLD and motion-induced signal changes occur in the same voxel.

“It should be noted, however, that there is a possibility of either missing activation or incorrectly estimating the response amplitude when the BOLD response and task-related motion-induced signal changes occur in the same voxel.”

The automatic speech condition successfully isolated fluency-related activations almost exclusively to the left hemisphere.

“Regardless of the interpretation of the automatic speech findings, this condition proved to be highly successful for isolating fluency-related activations nearly exclusively to the left hemisphere.”

The paradigm exploits the latency difference between the delayed BOLD response and motion artifact, reducing false positives from motion.

“This paradigm design exploits the latency difference between the delayed hemodynamic BOLD response and the motion artifact, minimizing the likelihood that motion artifacts appear as false positives (Birn et al., 2004).”

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The differences can be identified and evaluated when subjects speak aloud in a self-paced manner in the magnet.

“They also demonstrate that these differences can be identified and evaluated when subjects speak aloud in a self-paced manner in the magnet.”

The lack of prefrontal findings may relate to Baddeley et al.'s finding that switching costs are small when visual cues remove the need to remember switches.

“The lack of prefrontal findings in this study may also relate to the Baddeley et al (2001) finding that switching costs are small when the need to remember the switches is removed by providing visual cues.”

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The Gurd studies, like the current study, provide specific cues to switch.

“In contrast, the task used in the Gurd studies, like ours, provides specific cues to switch.”

Left hemisphere sites are involved in strategic lexical and semantic search and retrieval.

“In fact, in some of these regions, automatic speech resulted in almost no detectable BOLD response compared to rest, whereas the fluency tasks produced robust responses, consistent with claims that these left hemisphere sites are involved in strategic lexical and semantic search and retrieval processes (see Fig 1).”

The study shows that neuronal activation during overt self-paced verbal fluency can be assessed and separated from task-related motion effects using a block design with 10-second task and rest blocks.

“This study shows that neuronal activation during an overt self-paced verbal fluency task can be successfully assessed and separated from task-related motion effects by using a block design with task (speech) and rest (non-speech) block durations of 10s.”

Previous studies show that task-induced motion artifacts occur mainly in anterior inferior temporal lobes, orbitofrontal cortex, and brain edges.

“Previous studies have shown that these task-induced motion artifacts occur primarily in the anterior inferior temporal lobes, orbito-frontal cortex, and at the edges of the brain (Birn et al., 1998, 2004).”

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The study measured brain activity while subjects generated aloud lists to specific retrieval cues, more closely mirroring standard unpaced word generation than previous fMRI studies.

“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.”

The apparent conflict between the null middle frontal gyrus result and prior clinical research on prefrontal cortex during switching may reflect differences in task demands.

“The apparent conflict between this finding and previous clinical research emphasizing the role of prefrontal cortex during switching may reflect differences in task demands.”

• AssumptionRests on an assumption: Task switching requires increased attention, working memory, and other executive control processes.

The fMRI activations are consistent with the different requirements of letter and category fluency.

“Our fMRI data show activations consistent with these different requirements.”

• AssumptionRests on an assumption: Letter and category fluency share many cognitive processes, including sustained attention, search strategy, word selection, inhibition, working memory, and articulation.
• AssumptionRests on an assumption: Letter fluency requires orthographic selection and retrieval, while category fluency places greater demand on conceptual knowledge stores.

The posterior parietal activation during switching is consistent with previous covert verbal fluency studies.

“In addition, increased activation was observed in bilateral posterior parietal regions, a finding consistent with previous reports using covert verbal fluency tasks (Gurd et al., 2002; Gurd et al., 2003).”

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