C. Büchel

Multisubject fMRI Studies and Conjunction Analyses

In this paper we present an approach to making inferences about generic activations in groups of subjects using fMRI. In particular we suggest that activations common to all subjects reflect aspects of functional anatomy that may be typical of the population from which that group was sampled. These commonalities can be identified by a conjunction analysis of the activation effects in which the contrasts, testing for an activation, are specified separately for each subject. A conjunction is the joint refutation of multiple null hypotheses, in this instance, of no activation in any subject. The motivation behind this use of conjunctions is that fixed-effect analyses are generally more sensitive than equivalent random-effect analyses. This is because fixed-effect analyses can harness the large degrees of freedom and small scan-to-scan variability (relative to the variability in responses from subject to subject) when assessing the significance of an estimated response. The price one pays for the apparent sensitivity of fixed-effect analyses is that the ensuing inferences pertain to, and only to, the subjects studied. However, a conjunction analysis, using a fixed-effect model, allows one to infer: (i) that every subject studied activated and (ii) that at least a certain proportion of the population would have shown this effect. The second inference depends upon a meta-analytic formulation in terms of a confidence region for this proportion. This approach retains the sensitivity of fixed-effect analyses when the inference that only a substantial proportion of the population activates is sufficient.

Brain regions involved in articulation

BACKGROUNDnThe left inferior frontal gyrus (Brocas area) is generally believed to be critical for the motor act of speech. A lesion-based analysis has, however, shown that the left anterior insula is necessary for accurate articulation. We used functional imaging in normal people to show the neural systems involved in speech during different speech tasks.nnnMETHODSn12 normal people underwent positron emission tomography with oxygen-15-labelled water as tracer. We measured cerebral activity while participants performed three different tasks: repetition of heard nouns at different rates; listening to single nouns at different rates; and anticipation of listening or repetition. We analysed the data with imaging software.nnnFINDINGSnRepetition of single words did not activate Brocas area but activity in three left-lateralised regions was seen: the anterior insula, a localised region in the lateral premotor cortex, and the posterior pallidum. The left anterior insula and lateral premotor cortex showed a conjunction of activity for hearing and articulation. In addition, articulation modulated the response to hearing words in the left dorsolateral temporal cortex, the physiological expression of the speakers auditory attention being directed towards the stimuli and not his or her articulated responses.nnnINTERPRETATIONnThe formulation of an articulatory plan is a function of the left anterior insula and lateral premotor cortex and not of Brocas area. The left basal ganglia seem to be dominant for speech, although the axial muscles involved receive their motor output from both cerebral hemispheres.

Characterizing Stimulus-Response Functions Using Nonlinear Regressors in Parametric fMRI Experiments

Parametric study designs proved very useful in characterizing the relationship between experimental parameters (e.g., word presentation rate) and regional cerebral blood flow in positron emission tomography studies. In a previous paper we presented a method that fits nonlinear functions of stimulus or task parameters to hemodynamic responses, using second-order polynomial expansions. Here we expand this approach to model nonlinear relationships between BOLD responses and experimental parameters, using fMRI. We present a framework that allows this technique to be implemented in the context of the general linear model employed by statistical parametric mapping (SPM). Statistical inferences, in this instance, are based on F statistics and in this respect we emphasize the use of corrected P values for F fields (i.e., SPM¿F¿). The approach is illustrated with a fMRI study that looked at the effect of increasing auditory word-presentation rate. Our parametric design allowed us to characterize different forms of rate-dependent responses in three critical regions: (i) bilateral frontal regions showed a categorical response to the presence of words irrespective of rate, suggesting a role for this region in establishing cognitive (e.g., attentional) set; (ii) in bilateral occipitotemporal regions activations increased linearly with increasing word rate; and (iii) posterior auditory association cortex exhibited a nonlinear (inverted U) relationship to word rate.

A multimodal language region in the ventral visual pathway

Reading words and naming pictures involves the association of visual stimuli with phonological and semantic knowledge. Damage to a region of the brain in the left basal posterior temporal lobe (BA37), which is strategically situated between the visual cortex and the more anterior temporal cortex, leads to reading and naming deficits,. Additional evidence implicating this region in linguistic processing comes from functional neuroimaging studies of reading in normal subjects and subjects with developmental dyslexia,. Here we test whether the visual component of reading is essential for activation of BA37 by comparing cortical activations elicited by word processing in congenitally blind, late-blind and sighted subjects using functional neuroimaging. Despite the different modalities used (visual and tactile), all groups of subjects showed a common activation of BA37 by words relative to non-word letter-strings. These findings agree with the proposal that BA37 is an association area that integrates converging inputs from many regions. Our study confirms a prediction of theories of brain function that depend on convergence zones; the absence of one input (that is, visual) does not alter the response properties of such a convergence region.

Noun imageability and the temporal lobes

We used positron emission tomography to investigate brain activity in response to hearing or reading nouns of varying imageability. Three experiments were performed. Activity increased with noun imageability in the left mid-fusiform gyrus, the lateral parahippocampal area in humans, and in the rostral medial temporal lobes close to or within perirhinal cortex. The left mid-fusiform activation has been observed in previous imaging studies of single word processing. Its functional significance was variously attributed to semantic processing, visual imagery, encoding episodic memories, or the integration of lexical inputs from different sensory modalities. These hypotheses are not mutually exclusive. The more rostral medial lobe response to noun imageability has not been observed previously. However, lesions in perirhinal cortex impair knowledge about objects in non-human primates, and bilateral rostral ventromedial temporal lobe potentials in response to object nouns were observed with human intracranial recordings. Imageable (object) nouns are learnt with reference to sensory experiences of living and non-living objects, whereas acquisition of the meaning of low imageable (abstract) nouns is more dependent on their context within sentences. Parahippocampal and perirhinal cortices are reciprocally connected with, respectively, second and third order sensory association cortices. We conclude that access to the representations of word meaning is dependent on heteromodal temporal lobe cortex, and that during the acquisition of object nouns one route is established through ventromedial temporal cortical regions that have reciprocal connections with all sensory association cortices.

Event-related fMRI reveals cortical sites involved in contextual sentence integration.

We examined the effects of difficulty of sentential integration on blood oxygenation level-dependent contrast changes. Difficulty of integration was operationalized as the degree to which sentence-final nouns matched the expectations generated by preceding context. Nine young adults read short sentence fragments (e.g., The pilot flies.) which were completed by highly expected nouns (e.g., the plane), unexpected yet semantically legal nouns (e.g., the kite), nouns that violated the verbs selection restriction rules (e.g., the book), and pseudowords (e.g., the foop) and made quick lexical decisions on the sentence-final item. Overall, word completions resulted in higher changes in activation than pseudoword completions. The largest of those changes were observed in left angular and posterior middle temporal gyri, suggesting that despite the lexical nature of the task, word stimuli embedded in sentence contexts triggered integrative-semantic processes beyond a lexical level. A region-of-interest analysis in left inferior frontal and left posterior middle temporal areas revealed activation for both unexpected and anomalous completions when compared to expected completions. Thus, while the underlying processing mechanisms may differ, sentential integration appears similarly effortful for these two types of completions. Our findings are consistent with previous reports of local increases in activation as a function of (syntactic) complexity, while extending the findings to processing demands of semantic integration. Because of its sensitivity to changes in semantic congruence and the implicit nature of the task involved, we argue that the present paradigm is well suited to study patients with potential semantic deficits after brain damage.

Dynamic Changes in Effective Connectivity Characterized by Variable Parameter Regression and Kalman Filtering

Attention to visual motion can increase the responsiveness of the motion‐selective cortical area V5 and the posterior parietal cortex. We addressed attentional modulation of effective connectivity using variable parameter regression and functional magnetic resonance imaging. We present data from a single subject scanned under identical stimulus conditions (visual motion) while varying only the attentional component of the task. Variable parameter regression of the influence of V5 on PP revealed increased effective connectivity during attention to visual motion. With this dynamic measure of effective connectivity we were able to make inferences about the source of modulation by looking for regions that predicted the observed changes in connectivity. Using an ordinary regression analysis, we showed that activity in the prefrontal cortex could explain these changes and was sufficient to account for these modulatory influences on connections in the dorsal visual pathway. Hum. Brain Mapping 6:403–408, 1998.