Elizabeth Jefferies

Semantic processing in the anterior temporal lobes: A meta-analysis of the functional neuroimaging literature

The role of the anterior temporal lobes (ATLs) in semantic cognition is not clear from the current literature. Semantic dementia patients show a progressive and a specific semantic impairment, following bilateral atrophy of the ATLs. Neuroimaging studies of healthy participants, however, do not consistently show ATL activation during semantic tasks. Consequently, several influential theories of semantic memory do not ascribe a central role to the ATLs. We conducted a meta-analysis of 164 functional neuroimaging studies of semantic processing to investigate factors that might contribute to the inconsistency in previous results. Four factors influenced the likelihood of finding ATL activation: (1) the use of PET versus fMRI, reflecting the fact that fMRI but not PET is sensitive to distortion artifacts caused by large variations in magnetic susceptibility in the area of the ATL; (2) a field of view (FOV) of more than 15 cm, thereby ensuring whole-brain coverage; (3) the use of a high baseline task to prevent subtraction of otherwise uncontrolled semantic activation; (4) the inclusion of the ATL as an ROI. The type of stimuli or task did not influence the likelihood of ATL activation, consistent with the view that this region underpins an amodal semantic system. Spoken words, written words, and picture stimuli produced overlapping ATL peaks. On average, these were more inferior for picture-based tasks. We suggest that the specific pattern of ATL activation may be influenced by stimulus type due to variations across this region in the degree of connectivity with modality-specific areas in posterior temporal cortex.

The Ventral and Inferolateral Aspects of the Anterior Temporal Lobe Are Crucial in Semantic Memory: Evidence from a Novel Direct Comparison of Distortion-Corrected fMRI, rTMS, and Semantic Dementia

Although there is an emerging consensus that the anterior temporal lobes (ATLs) are involved in semantic memory, it is currently unclear which specific parts of this region are implicated in semantic representation. Answers to this question are difficult to glean from the existing literature for 3 reasons: 1) lesions of relevant patient groups tend to encompass the whole ATL region; 2) while local effects of repetitive transcranial magnetic stimulation (rTMS) are spatially more specific, only the lateral aspects of the ATL are available to stimulation; and 3) until recently, functional magnetic resonance imaging (fMRI) studies were hindered by technical limitations such as signal distortion and dropout due to magnetic inhomogeneities and also, in some cases, by methodological factors, including a restricted field of view and the choice of baseline contrast for subtraction analysis. By utilizing the same semantic task across semantic dementia, rTMS, and distortion-corrected fMRI in normal participants, we directly compared the results across the 3 methods for the first time. The findings were highly convergent and indicated that crucial regions within the ATL for semantic representation include the anterior inferior temporal gyrus, anterior fusiform gyrus, and the anterior superior temporal sulcus.

The Neural Organization of Semantic Control: TMS Evidence for a Distributed Network in Left Inferior Frontal and Posterior Middle Temporal Gyrus

Assigning meaning to words, sounds, and objects requires stored conceptual knowledge plus executive mechanisms that shape semantic retrieval according to the task or context. Despite the essential role of control in semantic cognition, its neural basis remains unclear. Neuroimaging and patient research has emphasized the importance of left inferior frontal gyrus (IFG)—however, impaired semantic control can also follow left temporoparietal lesions, suggesting that this function may be underpinned by a large-scale cortical network. We used repetitive transcranial magnetic stimulation in healthy volunteers to disrupt processing within 2 potential sites in this network—IFG and posterior middle temporal cortex. Stimulation of both sites selectively disrupted executively demanding semantic judgments: semantic decisions based on strong automatic associations were unaffected. Performance was also unchanged in nonsemantic tasks—irrespective of their executive demands—and following stimulation of a control site. These results reveal that an extended network of prefrontal and posterior temporal regions underpins semantic control.

Anterior temporal lobes mediate semantic representation: Mimicking semantic dementia by using rTMS in normal participants.

Studies of semantic dementia and PET neuroimaging investigations suggest that the anterior temporal lobes (ATL) are a critical substrate for semantic representation. In stark contrast, classical neurological models of comprehension do not include ATL, and likewise functional MRI studies often fail to show activations in the ATL, reinforcing the classical view. Using a novel application of low-frequency, repetitive transcranial magnetic stimulation (rTMS) over the ATL, we demonstrate that the behavioral pattern of semantic dementia can be mirrored in neurologically intact participants: Specifically, we show that temporary disruption to neural processing in the ATL produces a selective semantic impairment leading to significant slowing in both picture naming and word comprehension but not to other equally demanding, nonsemantic cognitive tasks.

Conceptual Knowledge Is Underpinned by the Temporal Pole Bilaterally: Convergent Evidence from rTMS

Conceptual knowledge provides the basis on which we bring meaning to our world. Studies of semantic dementia patients and some functional neuroimaging studies indicate that the anterior temporal lobes, bilaterally, are the core neural substrate for the formation of semantic representations. This hypothesis remains controversial, however, as traditional neurological models of comprehension do not posit a role for these regions. To adjudicate on this debate, we conducted 2 novel experiments that used off-line, low-frequency, repetitive transcranial magnetic stimulation to disrupt neural processing temporarily in the left or right temporal poles (TPs). The time required to make semantic decisions was slowed considerably, yet specifically, by this procedure. The results confirm that both TPs form a critical substrate within the neural network that supports conceptual knowledge.

Both the middle temporal gyrus and the ventral anterior temporal area are crucial for multimodal semantic processing: Distortion-corrected fmri evidence for a double gradient of information convergence in the temporal lobes

Most contemporary theories of semantic memory assume that concepts are formed from the distillation of information arising in distinct sensory and verbal modalities. The neural basis of this distillation or convergence of information was the focus of this study. Specifically, we explored two commonly posed hypotheses: (a) that the human middle temporal gyrus (MTG) provides a crucial semantic interface given the fact that it interposes auditory and visual processing streams and (b) that the anterior temporal region—especially its ventral surface (vATL)—provides a critical region for the multimodal integration of information. By utilizing distortion-corrected fMRI and an established semantic association assessment (commonly used in neuropsychological investigations), we compared the activation patterns observed for both the verbal and nonverbal versions of the same task. The results are consistent with the two hypotheses simultaneously: Both MTG and vATL are activated in common for word and picture semantic processing. Additional planned, ROI analyses show that this result follows from two principal axes of convergence in the temporal lobe: both lateral (toward MTG) and longitudinal (toward the anterior temporal lobe).

Category-specific versus category-general semantic impairment induced by transcranial magnetic stimulation.

Summary Semantic cognition permits us to bring meaning to our verbal and nonverbal experiences and to generate context- and time-appropriate behavior [1–2]. It is core to language and nonverbal skilled behaviors and, when impaired after brain damage, it generates significant disability [3]. A fundamental neuroscience question is, therefore, how does the brain code and generate semantic cognition? Historical and some contemporary theories emphasize that conceptualization stems from the joint action of modality-specific association cortices (the “distributed” theory) [4, 5] reflecting our accumulated verbal, motor, and sensory experiences. Parallel studies of semantic dementia, rTMS in normal participants, and neuroimaging indicate that the anterior temporal lobe (ATL) plays a crucial and necessary role in conceptualization by merging experience into an amodal semantic representation [1, 2, 6–8]. Some contemporary computational models suggest that concepts reflect a hub-and-spoke combination of information—modality-specific association areas support sensory, verbal, and motor sources (the spokes) while anterior temporal lobes act as an amodal hub. We demonstrate novel and striking evidence in favor of this hypothesis by applying rTMS to normal participants: ATL stimulation generates a category-general impairment whereas IPL stimulation induces a category-specific deficit for man-made objects, reflecting the coding of praxis in this neural region.

Going beyond inferior prefrontal involvement in semantic control: Evidence for the additional contribution of dorsal angular gyrus and posterior middle temporal cortex

Semantic cognition requires a combination of semantic representations and executive control processes to direct activation in a task- and time-appropriate fashion [Jefferies, E., & Lambon Ralph, M. A. Semantic impairment in stroke aphasia versus semantic dementia: A case-series comparison. Brain, 129, 2132–2147, 2006]. We undertook a formal meta-analysis to investigate which regions within the large-scale semantic network are specifically associated with the executive component of semantic cognition. Previous studies have described in detail the role of left ventral pFC in semantic regulation. We examined 53 studies that contrasted semantic tasks with high > low executive requirements to determine whether cortical regions beyond the left pFC show the same response profile to executive semantic demands. Our findings revealed that right pFC, posterior middle temporal gyrus (pMTG) and dorsal angular gyrus (bordering intraparietal sulcus) were also consistently recruited by executively demanding semantic tasks, demonstrating patterns of activation that were highly similar to the left ventral pFC. These regions overlap with the lesions in aphasic patients who exhibit multimodal semantic impairment because of impaired regulatory control (semantic aphasia)—providing important convergence between functional neuroimaging and neuropsychological studies of semantic cognition. Activation in dorsal angular gyrus and left ventral pFC was consistent across all types of executive semantic manipulation, regardless of whether the task was receptive or expressive, whereas pMTG activation was only observed for manipulation of control demands within receptive tasks. Second, we contrasted executively demanding tasks tapping semantics and phonology. Our findings revealed substantial overlap between the two sets of contrasts within left ventral pFC, suggesting this region underpins domain-general control mechanisms. In contrast, we observed relative specialization for semantic control within pMTG as well as the most ventral aspects of left pFC (BA 47), consistent with our proposal of a distributed network underpinning semantic control.

The neural and computational bases of semantic cognition

Semantic cognition refers to our ability to use, manipulate and generalize knowledge that is acquired over the lifespan to support innumerable verbal and non-verbal behaviours. This Review summarizes key findings and issues arising from a decade of research into the neurocognitive and neurocomputational underpinnings of this ability, leading to a new framework that we term controlled semantic cognition (CSC). CSC offers solutions to long-standing queries in philosophy and cognitive science, and yields a convergent framework for understanding the neural and computational bases of healthy semantic cognition and its dysfunction in brain disorders.

Comprehension of concrete and abstract words in semantic dementia

The vast majority of brain-injured patients with semantic impairment have better comprehension of concrete than abstract words. In contrast, several patients with semantic dementia (SD), who show circumscribed atrophy of the anterior temporal lobes bilaterally, have been reported to show reverse imageability effects, that is, relative preservation of abstract knowledge. Although these reports largely concern individual patients, some researchers have recently proposed that superior comprehension of abstract concepts is a characteristic feature of SD. This would imply that the anterior temporal lobes are particularly crucial for processing sensory aspects of semantic knowledge, which are associated with concrete not abstract concepts. However, functional neuroimaging studies of healthy participants do not unequivocally predict reverse imageability effects in SD because the temporal poles sometimes show greater activation for more abstract concepts. The authors examined a case-series of 11 SD patients on a synonym judgment test that orthogonally varied the frequency and imageability of the items. All patients had higher success rates for more imageable as well as more frequent words, suggesting that (1) the anterior temporal lobes underpin semantic knowledge for both concrete and abstract concepts, (2) more imageable items--perhaps because of their richer multimodal representations--are typically more robust in the face of global semantic degradation and (3) reverse imageability effects are not a characteristic feature of SD.