A number of neuroimaging findings have been interpreted as evidence that the left inferior frontal gyrus (IFG) subserves retrieval of semantic knowledge. We provide a fundamentally different interpretation, that it is not retrieval of semantic knowledge per se that is associated with left IFG activity but rather selection of information among competing alternatives from semantic memory. Selection demands were varied across three semantic tasks in a single group of subjects. Functional magnetic resonance imaging signal in overlapping regions of left IFG was dependent on selection demands in all three tasks. In addition, the degree of semantic processing was varied independently of selection demands in one of the tasks. The absence of left IFG activity for this comparison counters the argument that the effects of selection can be attributed solely to variations in degree of semantic retrieval. Our findings suggest that it is selection, not retrieval, of semantic knowledge that drives activity in the left IFG.What parts of the brain subserve the retrieval of semantic knowledge? A number of recent neuroimaging studies, using a range of different tasks, implicate the left inferior frontal gyrus (IFG) (1-8). Despite the impressive convergence of localizations across tasks as disparate as verb generation, stem completion, and abstract͞concrete judgments, the conclusion that semantic retrieval critically involves left IFG remains uncertain for two reasons. First, a smaller but still significant number of neuroimaging studies have failed to find left IFG activation during semantic retrieval tasks. For example, neither naming pictures nor verifying word associations consistently leads to left IFG activation, despite the prima facie involvement of semantic knowledge in both tasks (9, 10). Additionally, practice of a semantic retrieval task, even after just a single repetition, causes a marked decrease in left IFG activation (2,8). Second, neuropsychological studies of patient populations have so far failed to demonstrate the necessity of left IFG for semantic retrieval. Instead, impairments of semantic knowledge are most associated with temporal lobe pathology (11-13).The goal of this article is to propose and test an alternative interpretation of the activation of left IFG during semantic retrieval tasks, based on recent theorizing about the role of prefrontal cortex in nonsemantic domains. Cohen and ServanSchreiber (14) argued that prefrontal cortex enables flexible and context-sensitive responses, particularly in tasks where a response other than the prepotent one must be selected. Kimberg and Farah (15) characterized the role of prefrontal cortex in cognition as mediating the selection of action by the weighting of information active in working memory. When the contents of working memory are not critical for action selection, because the action is prepotent, or when the contents of working memory overwhelming support one action, then demands on prefrontal cortex are low. Their model implies that demands on pre...

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Over the last century, several dozen case reports have presented 'topographically disoriented' patients who, in some cases, appear to have selectively lost their ability to find their way within large-scale, locomotor environments. A review is offered here that has as its aim the creation of a taxonomy that accurately reflects the behavioural impairments and neuroanatomical findings of this literature. This effort is guided by an appreciation of the models of normative way-finding offered by environmental psychology and recent neuroscience research. It is proposed that several varieties of topographical disorientation exist, resulting from damage to distinct neuroanatomical areas. The particular pattern of impairments that patients evidence is argued to be consonant with the known functions of these cortical regions and with recent neuroimaging results. The conflicting claims of previous reviews of this area are also considered and addressed.

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Arterial spin labeling (ASL) perfusion fMRI data differ in important respects from the more familiar blood oxygen level-dependent (BOLD) fMRI data and require specific processing strategies. In this paper, we examined several factors that may influence ASL data analysis, including data storage bit resolution, motion correction, preprocessing for cerebral blood flow (CBF) calculations and nuisance covariate modeling. Continuous ASL data were collected at 3 T from 10 subjects while they performed a simple sensorimotor task with an epoch length of 48 s. These data were then analyzed using systematic variations of the factors listed above to identify the approach that yielded optimal signal detection for task activation. Improvements in statistical power were found for use of at least 10 bits for data storage at 3 T. No significant difference was found in motor cortex regarding using simple subtraction or sinc subtraction, but the former presented minor but significantly (P<.024) larger peak t value in visual cortex. While artifactual head motion patterns were observed in synthetic data and background-suppressed ASL data when label/control images were realigned to a common target, independent realignment of label and control images did not yield significant improvements in activation in the sensorimotor data. It was also found that CBF calculations should be performed prior to spatial normalization and that modeling of global fluctuations yielded significantly increased peak t value in motor cortex. The implementation of all ASL data processing approaches is easily accomplished within an open-source toolbox, ASLtbx, and is advocated for most perfusion fMRI data sets.