Functional MRI of Language in Aphasia: A Review of the Literature and the Methodological Challenges

Animal analogue studies show that damaged adult brains reorganize to accommodate compromised functions. In the human arena, functional magnetic resonance imaging (fMRI) and other functional neuroimaging techniques have been used to study reorganization of language substrates in aphasia. The resulting controversy regarding whether the right or the left hemisphere supports language recovery and treatment progress must be reframed. A more appropriate question is when left-hemisphere mechanisms and when right-hemisphere mechanisms support recovery of language functions. Small lesions generally lead to good recoveries supported by left-hemisphere mechanisms. However, when too much language eloquent cortex is damaged, right-hemisphere structures may provide the better substrate for recovery of language. Some studies suggest that recovery is particularly supported by homologues of damaged left-hemisphere structures. Evidence also suggests that under some circumstances, activity in both the left and right hemispheres can interfere with recovery of function. Further research will be needed to address these issues. However, daunting methodological problems must be managed to maximize the yield of future fMRI research in aphasia, especially in the area of language production. In this review, we cover six challenges for imaging language functions in aphasia with fMRI, with an emphasis on language production: (1) selection of a baseline task, (2) structure of language production trials, (3) mitigation of motion-related artifacts, (4) the use of stimulus onset versus response onset in fMRI analyses, (5) use of trials with correct responses and errors in analyses, and (6) reliability and stability of fMRI images across sessions. However, this list of methodological challenges is not exhaustive. Once methodology is advanced, knowledge from conceptually driven fMRI studies can be used to develop theoretically driven, mechanism-based treatments that will result in more effective therapy and to identify the best patient candidates for specific treatments. While the promise of fMRI in the study of aphasia is great, there is much work to be done before this technique will be a useful clinical tool.     

"Despair" induced by extinction trials in the water maze: relationship with measures of anxiety in aged and adult rats

We have previously reported that extinction of escape behavior in the water maze due to the removal of the platform coincided with the development of behavioral "despair" in aged and adult rats, as assessed by immobility. The present study examines further predictions derived from the hypothesis that the withholding of reinforcement induces behaviors akin to depression. We tested for correlations between extinction performance and immobility, as well as between immobility and measures of anxiety in aged and adult rats. Age comparisons were also performed on these variables. Forty aged and 29 adult male Wistar rats (24 and 3 months old, respectively) were examined in the open field, black/white box and elevated-plus maze followed by 6 days of training in the water maze hidden platform task and 8 days of extinction without the platform. Indices of immobility increased over trials of extinction, with the aged showing higher levels, earlier onsets and larger slope increases of immobility than the adults. A lower resistance-to-extinction was predictive of more "despair" in both age groups. Between-group differences in the open field, black/white box and elevated-plus maze indicated that the aged showed more anxiety-like behavior than the adults and/or explored these environments less. Within the aged group, indicators of fearfulness in the three tests were predictive of higher levels of "despair". The extinction-despair model is held to provide the promise of a conceptual and empirical model of human depression that is the consequence of withdrawal of reinforcement.     

Hippocampal long-term potentiation, memory, and longevity in mice that overexpress mitochondrial superoxide dismutase

Superoxide has been shown to be critically involved in several pathological manifestations of aging animals. In contrast, superoxide also can act as a signaling molecule to modulate signal transduction cascades required for hippocampal synaptic plasticity. Mitochondrial superoxide dismutase (SOD-2 or Mn-SOD) is a key antioxidant enzyme that scavenges superoxide. Thus, SOD-2 may not only prevent aging-related oxidative stress, but may also regulate redox signaling in young animals. We used transgenic mice overexpressing SOD-2 to study the role of mitochondrial superoxide in aging, synaptic plasticity, and memory-associated behavior. We found that overexpression of SOD-2 had no obvious effect on synaptic plasticity and memory formation in young mice, and could not rescue the age-related impairments in either synaptic plasticity or memory in old mice. However, SOD-2 overexpression did decrease mitochondrial superoxide in hippocampal neurons, and extended the lifespan of the mice. These findings increase our knowledge of the role of mitochondrial superoxide in physiological and pathological processes in the brain.     

Cross-task individual differences in error processing: Neural,electrophysiological, and genetic components

The error-related negativity (ERN) and error positivity (Pe) are electrophysiological markers of error processing thought to originate in the medial frontal cortex. Previous studies using probabilistic reinforcement showed that individuals who learn more from negative than from positive feedback (negative learners) had larger ERNs than did positive learners. These findings support the dopamine (DA) reinforcement-learning hypothesis of the ERN and associated computational models. However, it remains unclear (1) to what extent these effects generalize to tasks outside the restricted probabilistic reinforcement-learning domain and (2) whether there is a dopaminergic source of these effects. To address these issues, we tested subjects’ reinforcement-learning biases behaviorally and recorded EEG during an unrelated recognition memory experiment. Initial recognition responses were speeded, but the subjects were subsequently allowed to self-correct their responses. We found that negative learners, as assessed via probabilistic learning, had larger ERNs in the recognition memory task, suggestive of a common underlying enhanced error-processing mechanism. Negative learners also had enhanced Pes when selfcorrecting errors than did positive learners. Moreover, the ERN and Pe components contributed independently to negative learning. We also tested for a dopaminergic genetic basis of these ERP components. We analyzed the COMT val/met polymorphism, which has been linked to frontal DA levels. The COMT genotype affected Pe (but not ERN) magnitude; met/met homozygotes showed enhanced Pes to self-corrected errors, as compared with val carriers. These results are consistent with a role for the Pe and frontal monoamines in error awareness.     

Intentional Objects

The idea of an intentional object, or an object of thought, gives rise to a dilemma for theories of intentionality. Either intentional objects are existing objects, in which case it is impossible, contrary to appearances, to think about something which does not exist. Or some intentional objects are non-existent real objects. But this requires an obscure and implausible metaphysics. I argue that the way out of this dilemma is to deny that being an intentional object is being an entity of any kind. 'Object' here does not mean thing or entity. Rather, to say that something is an intentional object is just to say that it is an object of thought (or other intentional state or act) for a subject. It is further argued that theories of intentionality should not dispense with the idea of an intentional object.     

What's Really Wrong with the Limited Quantity View?

In Part Four of Reasons and Persons, Derek Parfit seeks Theory X – the Utilitarian account of the morality of choices where the number of people who will ever exist depends upon our actions. Parfit argues that X has yet to be found. The two simplest versions of Theory X are Total Utilitarianism and Average Utilitarianism. Unfortunately, Parfit argues, each of these leads to unacceptable results. Parfit explores various alternatives and finds them all unsatisfactory. This paper deals with one of those alternatives: the Limited Quantity View. I argue that ParfitÕs argument against this view fails. However, I then present a new and more general objection which defeats a broad range of utilitarian views, including the Limited Quantity View.     

Exclusion Problems and the Cardinality of Logical Space

Wittgenstein’s atomist picture, as embodied in his Tractatus, is initially very appealing. However, it faces the famous colour-exclusion problem. In this paper, I shall explain when the atomist picture can be defended (in principle) in the face of that problem; and, in the light of this, why the atomist picture should be rejected. I outline the atomist picture in Section 1. In Section 2, I present a very simple necessary and sufficient condition for the tenability (in principle) of the atomist picture. The condition is: logical space is a power of two. In Sections 3 and 4, I outline the colour-exclusion problem, and then show how the cardinality-condition supplies a response to exclusion problems. In Section 5, I explain how this amounts to a distillation of a proposal due to Moss (2012), which goes back to Carruthers (1990: 144–7). And in Section 6, I show how all this vindicates Wittgenstein’s ultimate rejection of the atomist picture. The brief reason is that we have no guarantee that there are any solutions to a given exclusion problem but, if there are any, then there are far too many.     

The Philosophical Use and Misuse of Science

Science is our best way of finding out about the natural world, and philosophers who write about that world ought to be sensitive to the claims of our best science. There are obstacles, however, to outsiders using science well. We think philosophers are prone to misuse science: to give undue weight to results that are untested; to highlight favorable and ignore unfavorable data; to give illegitimate weight to the authority of science; to leap from scientific premises to philosophical conclusions without spelling out their relevance; to treat mere resonance between a scientific theory and a philosophical view as empirical evidence for the philosophical view. This article identifies and illustrates some of the ways in which philosophers misuse science, explains why these pitfalls are easy to fall into, and concludes with suggestions for avoiding them.     

Nostalgia in response to group‐based exclusion: The role of attachment‐related avoidance

We proposed that nostalgia, by virtue of its sociality, can be an indirect strategy to counteract relational deficiencies stemming from group‐based exclusion. We instructed Greek participants to recall an event in which they experienced exclusion on the basis of their nationality versus a control event. We anticipated that participants would react to group‐based exclusion with increased nostalgia. Specifically, because low attachment‐related avoidance facilitates proximity‐seeking in response to distress, we hypothesized that group‐based exclusion would increase nostalgia (a form of proximity‐seeking) more strongly when avoidance is low. Results supported this moderation hypothesis. In turn, increased nostalgia in response to group‐based exclusion predicted stronger ingroup identification. For low‐avoidants, then, group‐based exclusion fortified ingroup identification via increased nostalgia (moderated mediation).