Jeffrey R. Binder

Where Is the Semantic System? A Critical Review and Meta-Analysis of 120 Functional Neuroimaging Studies

Semantic memory refers to knowledge about people, objects, actions, relations, self, and culture acquired through experience. The neural systems that store and retrieve this information have been studied for many years, but a consensus regarding their identity has not been reached. Using strict inclusion criteria, we analyzed 120 functional neuroimaging studies focusing on semantic processing. Reliable areas of activation in these studies were identified using the activation likelihood estimate (ALE) technique. These activations formed a distinct, left-lateralized network comprised of 7 regions: posterior inferior parietal lobe, middle temporal gyrus, fusiform and parahippocampal gyri, dorsomedial prefrontal cortex, inferior frontal gyrus, ventromedial prefrontal cortex, and posterior cingulate gyrus. Secondary analyses showed specific subregions of this network associated with knowledge of actions, manipulable artifacts, abstract concepts, and concrete concepts. The cortical regions involved in semantic processing can be grouped into 3 broad categories: posterior multimodal and heteromodal association cortex, heteromodal prefrontal cortex, and medial limbic regions. The expansion of these regions in the human relative to the nonhuman primate brain may explain uniquely human capacities to use language productively, plan, solve problems, and create cultural and technological artifacts, all of which depend on the fluid and efficient retrieval and manipulation of semantic knowledge.

Human Brain Language Areas Identified by Functional Magnetic Resonance Imaging

Functional magnetic resonance imaging (FMRI) was used to identify candidate language processing areas in the intact human brain. Language was defined broadly to include both phonological and lexical–semantic functions and to exclude sensory, motor, and general executive functions. The language activation task required phonetic and semantic analysis of aurally presented words and was compared with a control task involving perceptual analysis of nonlinguistic sounds. Functional maps of the entire brain were obtained from 30 right-handed subjects. These maps were averaged in standard stereotaxic space to produce a robust “average activation map” that proved reliable in a split-half analysis. As predicted from classical models of language organization based on lesion data, cortical activation associated with language processing was strongly lateralized to the left cerebral hemisphere and involved a network of regions in the frontal, temporal, and parietal lobes. Less consistent with classical models were (1) the existence of left hemisphere temporoparietal language areas outside the traditional “Wernicke area,” namely, in the middle temporal, inferior temporal, fusiform, and angular gyri; (2) extensive left prefrontal language areas outside the classical “Broca area”; and (3) clear participation of these left frontal areas in a task emphasizing “receptive” language functions. Although partly in conflict with the classical model of language localization, these findings are generally compatible with reported lesion data and provide additional support for ongoing efforts to refine and extend the classical model.

A Parametric Manipulation of Factors Affecting Task-induced Deactivation in Functional Neuroimaging

Task-induced deactivation (TID) refers to a regional decrease in blood flow during an active task relative to a resting or passive baseline. We tested the hypothesis that TID results from a reallocation of processing resources by parametrically manipulating task difficulty within three factors: target discriminability, stimulus presentation rate, and short-term memory load. Subjects performed an auditory target detection task during functional magnetic resonance imaging (fMRI), responding to a single target tone or, in the short-term memory load conditions, to target sequences. Seven task conditions (a common version and two additional levels for each of the three factors) were each alternated with rest in a block design. Analysis of covariance identified brain regions in which TID occurred. Analyses of variance identified seven regions (left anterior cingulate/superior frontal gyrus, left middle frontal gyrus, right anterior cingulate gyrus, left and right posterior cingulate gyrus, left posterior parieto-occipital cortex, and right precuneus) in which TID magnitude varied across task levels within a factor. Follow-up tests indicated that for each of the three factors, TID magnitude increased with task difficulty. These results suggest that TID represents reallocation of processing resources from areas in which TID occurs to areas involved in task performance. Short-term memory load and stimulus rate also predict suppression of spontaneous thought, and many of the brain areas showing TID have been linked with semantic processing, supporting claims that TID may be due in part to suspension of spontaneous semantic processes that occur during rest (Binder et al., 1999). The concept that the typical resting state is actually a condition characterized by rich cognitive activity has important implications for the design and analysis of neuroimaging studies.

Functional magnetic resonance imaging of complex human movements

Functional magnetic resonance imaging (FMRI) is a new, noninvasive imaging tool thought to measure changes related to regional cerebral blood flow (rCBF). Previous FMRI studies have demonstrated functional changes within the primary cerebral cortex in response to simple activation tasks, but it is unknown whether FMRI can also detect changes within the nonprimary cortex in response to complex mental activities. We therefore scanned six right-handed healthy subjects while they performed self-paced simple and complex finger movements with the right and left hands. Some subjects also performed the tasks at a fixed rate (2 Hz) or imagined performing the complex task. Functional changes occurred (1) in the contralateral primary motor cortex during simple, self-paced movements; (2) in the contralateral (and occasionally ipsilateral) primary motor cortex, the supplementary motor area (SMA), the premotor cortex of both hemispheres, and the contralateral somatosensory cortex during complex, self-paced movements; (3) with less intensity during paced movements, presumably due to the slower movement rates associated with the paced (relative to self-paced) condition; and (4) in the SMA and, to a lesser degree, the premotor cortex during imagined complex movements. These preliminary results are consistent with hierarchical models of voluntary motor control.

The neurobiology of semantic memory

Semantic memory includes all acquired knowledge about the world and is the basis for nearly all human activity, yet its neurobiological foundation is only now becoming clear. Recent neuroimaging studies demonstrate two striking results: the participation of modality-specific sensory, motor, and emotion systems in language comprehension, and the existence of large brain regions that participate in comprehension tasks but are not modality-specific. These latter regions, which include the inferior parietal lobe and much of the temporal lobe, lie at convergences of multiple perceptual processing streams. These convergences enable increasingly abstract, supramodal representations of perceptual experience that support a variety of conceptual functions including object recognition, social cognition, language, and the remarkable human capacity to remember the past and imagine the future.

Neural correlates of sensory and decision processes in auditory object identification.

Physiological studies of auditory perception have not yet clearly distinguished sensory from decision processes. In this experiment, human participants identified speech sounds masked by varying levels of noise while blood oxygenation signals in the brain were recorded with functional magnetic resonance imaging (fMRI). Accuracy and response time were used to characterize the behavior of sensory and decision components of this perceptual system. Oxygenation signals in a cortical subregion just anterior and lateral to primary auditory cortex predicted accuracy of sound identification, whereas signals in an inferior frontal region predicted response time. Our findings provide neurophysiological evidence for a functional distinction between sensory and decision mechanisms underlying auditory object identification. The present results also indicate a link between inferior frontal lobe activation and response-selection processes during auditory perception tasks.

Distinct Brain Systems for Processing Concrete and Abstract Concepts

Behavioral and neurophysiological effects of word imageability and concreteness remain a topic of central interest in cognitive neuroscience and could provide essential clues for understanding how the brain processes conceptual knowledge. We examined these effects using event-related functional magnetic resonance imaging while participants identified concrete and abstract words. Relative to nonwords, concrete and abstract words both activated a left-lateralized network of multimodal association areas previously linked with verbal semantic processing. Areas in the left lateral temporal lobe were equally activated by both word types, whereas bilateral regions including the angular gyrus and the dorsal prefrontal cortex were more strongly engaged by concrete words. Relative to concrete words, abstract words activated left inferior frontal regions previously linked with phonological and verbal working memory processes. The results show overlapping but partly distinct neural systems for processing concrete and abstract concepts, with greater involvement of bilateral association areas during concrete word processing, and processing of abstract concepts almost exclusively by the left hemisphere.

Language lateralization in left-handed and ambidextrous people fMRI data

Background It is generally accepted that most people have left-hemispheric language dominance, though the actual incidence of atypical language distribution in non–right-handed subjects has not been extensively studied. The authors examined language distribution in these subjects and evaluated the relationships between personal handedness, family history of sinistrality, and a language laterality index (LI) measured with fMRI. Methods The authors used whole-brain fMRI to examine 50 healthy, non–right-handed subjects (Edinburgh Handedness Inventory quotient between −100 and 52) while they performed language activation and nonlinguistic control tasks. Counts of active voxels (p < 0.001) were computed in 22 regions of interest (ROI) covering both hemispheres and the cerebellum. LI were calculated for each ROI and each entire hemisphere using the formula [L − R]/[L + R]. Results Activation was predominantly right hemispheric in 8% (4/50), symmetric in 14% (7/50), and predominantly left hemispheric in 78% (39/50) of the subjects. Lateralization patterns were similar for all hemispheric ROI. Associations were observed between personal handedness and LI (r = 0.28, p = 0.046), family history of sinistrality and LI (p = 0.031), and age and LI (r = −0.49, p < 0.001). Conclusions The incidence of atypical language lateralization in normal left-handed and ambidextrous subjects is higher than in normal right-handed subjects (22% vs 4–6%). These whole-brain results confirm previous findings in a left-handed cohort studied with fMRI of the lateral frontal lobe. Associations observed between personal handedness and LI and family history of handedness and LI may indicate a common genetic factor underlying the inheritance of handedness and language lateralization.

Relationship Between Finger Movement Rate and Functional Magnetic Resonance Signal Change in Human Primary Motor Cortex

Functional magnetic resonance imaging (FMRI) is a noninvasive technique for mapping regional brain changes in response to sensory, motor, or cognitive activation tasks. Interpretation of these activation experiments may be confounded by more elementary task parameters, such as stimulus presentation or movement rates. We examined the effect of movement rate on the FMRI response recorded from the contralateral primary motor cortex. Four right-handed healthy subjects performed flexion-extension movements of digits 2–5 of the right hand at rates of 1, 2, 3, 4, or 5 Hz. Results of this study indicated a positive linear relationship between movement rate and FMRI signal change. Additionally, the number of voxels demonstrating functional activity increased significantly with faster movement rates. The magnitude of the signal change at each movement rate remained constant over the course of three 8-min scanning series. These findings are similar to those of previous rate studies of the visual and auditory system performed with positron emission tomography (PET) and FMRI.

Neural Basis of Endogenous and Exogenous Spatial Orienting: A Functional MRI Study

Whole-brain functional magnetic resonance imaging (MRI) was used to examine the neural substrates of internally (endogenous) and externally (exogenous) induced covert shifts of attention. Thirteen normal subjects performed three orienting conditions: endogenous (location of peripheral target predicted by a central arrow 80 of the time), exogenous (peripheral target preceded by a noninformative peripheral cue), and control (peripheral target preceded by noninformative central cue). Behavioral results indicated faster reaction times (RTs) for valid than for invalid trials for the endogenous condition but slower RTs for valid than for invalid trials for the exogenous condition (inhibition of return). The spatial extent and intensity of activation was greatest for the endogenous condition, consistent with the hypothesis that endogenous orienting is more effortful (less automatic) than exogenous orienting. Overall, we did not observe distinctly separable neural systems associated with the endogenous and exogenous orienting conditions. Both exogenous and endogenous orienting, but not the control condition, activated bilateral parietal and dorsal premotor regions, including the frontal eye fields. These results suggest a specific role for these regions in preparatory responding to peripheral stimuli. The right dorsolateral prefrontal cortex (BA 46) was activated selectively by the endogenous condition. This finding suggests that voluntary, but not reflexive, shifts of attention engage working memory systems.