Inferring resting-state connectivity patterns from functional magnetic resonance imaging (fMRI) data is a challenging task for any analytical technique. In this paper, we review a probabilistic independent component analysis (PICA) approach, optimized for the analysis of fMRI data, and discuss the role which this exploratory technique can take in scientific investigations into the structure of these effects. We apply PICA to fMRI data acquired at rest, in order to characterize the spatio-temporal structure of such data, and demonstrate that this is an effective and robust tool for the identification of low-frequency resting-state patterns from data acquired at various different spatial and temporal resolutions. We show that these networks exhibit high spatial consistency across subjects and closely resemble discrete cortical functional networks such as visual cortical areas or sensory-motor cortex.

The ventral occipitotemporal cortex (vOT) is involved in the perception of visually presented objects and written words. The Interactive Account of vOT function is based on the premise that perception involves the synthesis of bottom-up sensory input with top-down predictions that are generated automatically from prior experience. We propose that vOT integrates visuospatial features abstracted from sensory inputs with higher level associations such as speech sounds, actions and meanings. In this context, specialization for orthography emerges from regional interactions without assuming that vOT is selectively tuned to orthographic features. We discuss how the Interactive Account explains left vOT responses during normal reading and developmental dyslexia; and how it accounts for the behavioural consequences of left vOT damage.

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The involvement of the left inferior prefrontal cortex (LIPC) in phonological processing is well established from both lesion-deficit studies with neurological patients and functional neuroimaging studies of normals. Its involvement in semantic processing, on the other hand, is less clear. Although many imaging studies have demonstrated LIPC activation during semantic tasks, this may be due to implicit phonological processing. This article presents two experiments investigating semantic functions in the LIPC. Results from a functional magnetic resonance imaging experiment demonstrated that both semantic and phonological processing activated a common set of areas within this region. In addition, there was a reliable increase in activation for semantic relative to phonological decisions in the anterior LIPC while the opposite comparison (phonological vs. semantic decisions) revealed an area of enhanced activation within the posterior LIPC. A second experiment used transcranial magnetic stimulation (TMS) to temporarily interfere with neural information processing in the anterior portion of the LIPC to determine whether this region was essential for normal semantic performance. Both repetitive and single pulse TMS significantly slowed subjects' reactions for the semantic but not for the perceptual control task. Our results clarify the functional anatomy of the LIPC by demonstrating that anterior and posterior regions contribute to both semantic and phonological processing, albeit to different extents. In addition, the findings go beyond simply establishing a correlation between semantic processing and activation in the LIPC and demonstrate that a transient disruption of processing selectively interfered with semantic processing.

It is generally assumed that abstract concepts are linguistically coded, in line with imaging evidence of greater engagement of the left perisylvian language network for abstract than concrete words (Binder JR, Desai RH, Graves WW, Conant LL. 2009. Where is the semantic system? A critical review and meta-analysis of 120 functional neuroimaging studies. Cerebral Cortex. 19:2767-2796; Wang J, Conder JA, Blitzer DN, Shinkareva SV. 2010. Neural representation of abstract and concrete concepts: A meta-analysis of neuroimaging studies. Hum Brain Map. 31:1459-1468). Recent behavioral work, which used tighter matching of items than previous studies, however, suggests that abstract concepts also entail affective processing to a greater extent than concrete concepts (Kousta S-T, Vigliocco G, Vinson DP, Andrews M, Del Campo E. The representation of abstract words: Why emotion matters. J Exp Psychol Gen. 140:14-34). Here we report a functional magnetic resonance imaging experiment that shows greater engagement of the rostral anterior cingulate cortex, an area associated with emotion processing (e.g., Etkin A, Egner T, Peraza DM, Kandel ER, Hirsch J. 2006. Resolving emotional conflict: A role for the rostral anterior cingulate cortex in modulating activity in the amygdala. Neuron. 52:871), in abstract processing. For abstract words, activation in this area was modulated by the hedonic valence (degree of positive or negative affective association) of our items. A correlation analysis of more than 1,400 English words further showed that abstract words, in general, receive higher ratings for affective associations (both valence and arousal) than concrete words, supporting the view that engagement of emotional processing is generally required for processing abstract words. We argue that these results support embodiment views of semantic representation, according to which, whereas concrete concepts are grounded in our sensory-motor experience, affective experience is crucial in the grounding of abstract concepts.

Category-specific semantic impairments have been explained in terms of preferential damage to different types of features (e.g., perceptual vs. functional). This account is compatible with cases in which the impairments were the result of relatively focal lesions, as in herpes encephalitis. Recently, however, there have been reports of category-specific impairments associated with Alzheimer's disease, in which there is more widespread, patchy damage. We present experiments with a connectionist model that show how "category-specific" impairments can arise in cases of both localized and widespread damage; in this model, types of features are topographically organized, but specific categories are not. These effects mainly depend on differences between categories in the distribution of correlated features. The model's predictions about degree of impairment on natural kinds and artifacts over the course of semantic deterioration are shown to be consistent with existing patient data. The model shows how the probabilistic nature of damage in Alzheimer's disease interacts with the structure of semantic memory to yield different patterns of impairment between patients and categories over time.

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Our ability to judge the consequences of our actions is central to rational decision making. A large body of evidence implicates primate prefrontal regions in the regulation of this ability. It has proven extremely difficult, however, to separate functional areas in the frontal lobes. Using functional magnetic resonance imaging, we demonstrate complementary and reciprocal roles for the human orbitofrontal (OFC) and dorsal anterior cingulate cortices (ACd) in monitoring the outcome of behavior. Activation levels in these regions were negatively correlated, with activation increasing in the ACd and decreasing in the OFC when the selected response was the result of the participant's own decision. The pattern was reversed when the selected response was guided by the experimenter rather than the participant. These results indicate that the neural mechanisms underlying the way we assess the consequences of choices differ depending on whether we are told what to do or are able to exercise our volition.