Remediation of deficits affecting different components of the spelling process

Background: There have been relatively few studies concerned with the treatment of spelling deficits. Among these, there have been a small number that have targeted specific components of the spelling process. Although most of these studies report success using treatments that involve repeated spelling and/or copy, the results have been mixed, especially as concerns the generalisation of treatment benefits to untreated items. Aims: This investigation was designed to examine the responsiveness to the same treatment protocol of deficits affecting different cognitive mechanisms of the spelling process. Methods & Procedures: We applied the same delayed-copy treatment protocol to two individuals with selective deficits of the orthographic output lexicon and the graphemic buffer. The two individuals were otherwise matched in terms of the severity of their deficits and their general cognitive profiles. Outcomes & Results: Both individuals exhibited long-lasting word-specific benefits from the treatment. However, they differed in that the graphemic buffer deficit exhibited generalisation to untreated words, whereas the orthographic output lexicon did not. Conclusions: The absence of presence of generalisation effects in response to the successful treatment of target items is determined by the specific cognitive component/s that constitute the source of the deficit.     

The temporal interaction of modality specific and process specific neural networks supporting simple working memory tasks

Several theories of brain function emphasize distinctions between sensory and cognitive systems. We hypothesized, instead, that sensory and cognitive systems interact to instantiate the task at the neural level. We tested whether input modality interacts with working memory operations in that, despite similar cognitive demands, differences in the anatomical locations or temporal dynamics of activations following auditory or visual input would not be limited to the sensory cortices. We recorded event-related brain potentials (ERPs) while participants performed simple short-term memory tasks involving visually or auditorily presented bandpass-filtered noise stimuli. Our analyses suggested that working memory operations in each modality had a very similar spatial distribution of current sources outside the sensory cortices, but differed in terms of time course. Specifically, information for visual processing was updated and held online in a manner that was different from auditory processing, which was done mostly after the offset of the final stimulus. Our results suggest that the neural networks that support working memory operations have different temporal dynamics for auditory and visual material, even when the stimuli are matched in term of discriminability, and are designed to undergo very similar transformations when they are encoded and retrieved from memory.     

Further evidence about the crucial role of CSF biomarkers in diagnosis of posterior cortical atrophy

Cerebrospinal fluid (CSF) biomarkers (protein tau, phosphorylated tau and amyloid Beta 1–42) are recognized as a supportive feature in diagnosis of Alzheimer’s disease (AD) and their role in identifying atypical variants of AD is currently under investigation. We dosed these proteins in nine patients clinically and instrumentally affected by posterior cortical atrophy (PCA), a rare disorder characterized by a progressive neurodegenerative process that involves primarily the posterior brain regions. We compared the obtained values with a large group of AD patients (N = 117), recruited in our neurological department. Our data revealed no differences in the CSF profile between PCA and AD, showing abnormal values of protein tau, phosphorylated tau and amyloid Beta 1–42 in both groups of patients. This study underlines the diagnostic importance of CSF biomarkers in PCA patients, supporting the hypothesis that PCA is an atypical variant of AD with an onset before the age of 65.     

A specific role for posterior dorsolateral striatum in human habit learning

Habits are characterized by an insensitivity to their consequences and, as such, can be distinguished from goal-directed actions. The neural basis of the development of demonstrably outcome-insensitive habitual actions in humans has not been previously characterized. In this experiment, we show that extensive training on a free-operant task reduces the sensitivity of participants' behavior to a reduction in outcome value. Analysis of functional magnetic resonance imaging data acquired during training revealed a significant increase in task-related cue sensitivity in a right posterior putamen–globus pallidus region as training progressed. These results provide evidence for a shift from goal-directed to habit-based control of instrumental actions in humans, and suggest that cue-driven activation in a specific region of dorsolateral posterior putamen may contribute to the habitual control of behavior in humans.     

The role of semantics in reading and spelling: evidence for the 'summation hypothesis'

This study documents a patient, SA, with an impairment of semantic memory arising as a result of Semantic Dementia (Pick's disease). The patient is impaired at deriving semantic knowledge from both words and pictures. However, his ability to derive semantic knowledge of countries is relatively spared compared to concrete nouns and famous people. The presence of a semantic deficit was used to investigate the role of semantics in reading and spelling. Several novel cueing/priming paradigms are reported which suggest that SA is able to use partial semantic knowledge to constrain his reading and spelling. These results are broadly consistent with the 'summation hypothesis' [27] and suggest that normal reading and spelling may take place by integrating both semantic information and knowledge of direct orthography-phonology correspondences.     

The role of the posterior fusiform gyrus in reading

Studies of skilled reading [Price, C. J., & Mechelli, A. Reading and reading disturbance. Current Opinion in Neurobiology, 15, 231-238, 2005], its acquisition in children [Shaywitz, B. A., Shaywitz, S. E., Pugh, K. R., Mencl, W. E., Fulbright, R. K., Skudlarski, P., et al. Disruption of posterior brain systems for reading in children with developmental dyslexia. Biological Psychiatry, 52, 101-110, 2002; Turkeltaub, P. E., Gareau, L., Flowers, D. L., Zeffiro, T. A., & Eden, G. F. Development of neural mechanisms for reading. Nature Neuroscience, 6, 767-773, 2003], and its impairment in patients with pure alexia [Leff, A. P., Crewes, H., Plant, G. T., Scott, S. K., Kennard, C., & Wise, R. J. The functional anatomy of single word reading in patients with hemianopic and pure alexia. Brain, 124, 510-521, 2001] all highlight the importance of the left posterior fusiform cortex in visual word recognition. We used visual masked priming and functional magnetic resonance imaging to elucidate the specific functional contribution of this region to reading and found that (1) unlike words, repetition of pseudowords ("solst-solst") did not produce a neural priming effect in this region, (2) orthographically related words such as "corner-corn" did produce a neural priming effect, but (3) this orthographic priming effect was reduced when prime-target pairs were semantically related ("teacher-teach"). These findings conflict with the notion of stored visual word forms and instead suggest that this region acts as an interface between visual form information and higher order stimulus properties such as its associated sound and meaning. More importantly, this function is not specific to reading but is also engaged when processing any meaningful visual stimulus.     

The crucial role of psychodynamic understanding in the treatment of eating disorders.

Psychodynamic interventions for eating-disordered patients can provide a unique pathway to understanding the illness. Contemporary practice strives to integrate insights derived from drive theory, ego psychology, object relations, self-psychology, relational and attachment theories, and intersubjectivity to claim a more thorough understanding of the antecedents of the eating-disorder symptoms. Placing emphasis on the unique personal history of the individual and finding a safe haven in which to process that history are cornerstones of psychodynamic treatment embraced by each of these schools of thought. This article has emphasized the importance of creating a safe space for these patients to speak, processing the most salient affects that arise in the therapeutic dyad, assessing potential transference and counter-transference paradigms, and assisting these patients in mastering symptomatic behaviors by making healthier identifications with their therapists. Although the selected topics merely sketch how psychodynamic treatment may apply in some cases, it is hoped that they will whet the appetite for a more sustained inquiry for readers. Contemporary psychoanalysis aims to be more "user-friendly" for patients and treaters and eschews a "one interpretation fits all" approach to any person suffering from a particular diagnosis. Attachment theory, infant and developmental studies, and in-depth outcomes research are shaping the way that psychoanalytically informed treatments are carried out. Within the next decade, insights derived from these kinds of psychoanalytic research will be even more concretely and meaningfully used in the treatment of eating disorders and other Axis I conditions.     

The rat medial frontal cortex projects directly to autonomic regions of the brainstem

Pressure injections of the anterograde tracer wheat germ agglutinin conjugated with horseradish peroxidase (WGA-HRP) into the infralimbic (IL) and prelimbic (PL) regions of the medial frontal cortex of the rat produced anterograde, terminal-like labeling in the lateral dorsal tegmental nucleus (LDTg) of the dorsal pons and the ventral, ventrolateral, intermediate, medial and commissural subnuclei of the nucleus of the solitary nucleus (NTS) in the dorsomedial medulla. Injections involving IL resulted in heavier labeling than the labeling seen after PL injections only. The LDTg has been described as the pontine micturition center, involved in the micturition reflex. The possible role that the projections to the LDTg may play in fluid homeostasis is discussed. The labeled NTS subnuclei receive visceral afferent inputs from the heart, baroreceptors, lungs and gut. The direct cortical projections to these areas may be involved in mediating the bradycardia, depressor responses, and changes in respiratory and gastric activity which are seen after electrical stimulation of the rat medial frontal cortex. The present data support the concept that the infralimbic and prelimbic cortices function as a "visceral motor" cortex, involved in control of a variety of autonomic functions.     

The role of the medial frontal cortex in the maintenance of emotional states

Evidence is accruing that people can maintain their emotional states, but how they do it and which brain regions are responsible still remains unclear. We examined whether people maintain emotional states ‘actively’, with explicit elaboration of the emotion, or ‘passively’, without elaboration. Twenty-four participants completed an emotion maintenance task in which they either maintained the emotional intensity from the first picture of a pair to compare to that of the second picture (‘maintain’ condition), or only rated their emotional response to the second picture (‘non-maintain’ condition). Supporting the ‘active’ maintenance hypothesis, when maintaining vs not maintaining emotion, participants exhibited increased height and width of activation in the dorsal medial frontal cortex (MFC) and lateral prefrontal cortex, regions associated with explicit emotion generation and manipulation of contents in working memory, respectively. Supporting the ‘passive’ maintenance hypothesis, however, when viewing negative emotional pictures (vs neutral pictures) that were not explicitly maintained, participants exhibited greater duration of activity in the rostral MFC, a region associated with implicit emotion generation. Supported by behavioral findings, this evidence that people maintain emotional states both naturally in the rMFC and strategically in the dMFC may be critical for understanding normal as well as disordered emotion regulation.     

The role of inferior frontal gyrus in processing Chinese classifiers

The Chinese classifier system classifies nouns and builds a relation between classifiers and their corresponding nouns. This functional magnetic resonance imaging (fMRI) study examined brain activation of Chinese classifiers during reading comprehension. Thirty-four participants read and performed semantic congruency judgments on congruent, inside-classifier (IC) violated, and outside-classifier (OC) violated sentences. The IC and OC violations were created by changing the correct classifier to an inappropriate classifier and a non-classifier, respectively. The comparison of the IC violation vs. the congruent condition produced greater activation in the mid-ventral region (BA 45) of the left inferior frontal gyrus (IFG), suggesting an increased demand on semantic processing. Contrasting different subtypes of IC violation produced greater activation in the right IFG (BAs 45 and 47), indicating that processing mass/count classifiers involves distinct brain activations. The OC violation produced greater activation in the left IFG (BAs 45 and 44), suggesting both semantic and syntactic processing. These results indicate that different parts of the IFG contribute to syntactic and semantic processing of classifier phrases in reading Chinese for comprehension.     

The specific role of chemokines in atherosclerosis

Atherosclerosis is a chronic inflammatory disease that represents the primary cause of heart disease and stroke. The recruitment of inflammatory cells in the intima is an essential step in the development and progression of atherosclerosis. This process is triggered by local production of chemokines and chemokine receptors from activated endothelial cells and inflammatory cells. Various members of the CC chemokine family (e.g. MCP-1/CCL2) as well as CXC family (e.g. IL-8/CCL8, IP-10/CXCL10, SDF-1/CXCL12) and, more recently, fractalkine/CX3CL1 have been implicated in atherosclerosis development. Latest findings in animal models suggest that blocking chemokine/chemokine receptor interactions may serve as a suitable approach to treat atherosclerosis. Likewise, chemokine antagonists that inhibit leukocyte recruitment could particularly be interesting to treat inflammation in response to myocardial infarction, the major consequence of atherosclerosis.     

Functional connectivity separates switching operations in the posterior lateral frontal cortex

Task representations consist of different aspects such as the representations of the relevant stimuli, the abstract rules to be applied, and the actions to be performed. To be flexible in our daily lives, we frequently need to switch between some or all aspects of a task. In the present study, we examined whether switching between abstract task rules and switching between response hands is associated with overlapping regions in the posterior lateral frontal cortex and whether switching between these two aspects of a task representation is neurally implemented by distinct functional brain networks. Subjects performed a cue-based task-switching paradigm where the location of the task cue additionally specified the response hand to be used. Overlapping activity for switching between abstract rules versus response hands was present in the inferior frontal junction area of the posterolateral frontal cortex. This region, however, showed very distinct patterns of functional connectivity depending on the content of the switch: Increased functional connectivity with anterior prefrontal, superior frontal, and hippocampal regions was present for abstract rule switching, whereas response hand switching led to increased coupling with motor regions surrounding the central sulcus. These results reveal that a rather general involvement of the posterior lateral frontal cortex in different switching contexts can be further characterized by highly specific functional interactions with other task-relevant regions, depending on the content of the switch.     

The role of the frontal cortex in the mouse in behavioral sensitization to amphetamine

Pharmacological studies have shown that a variety of neuroeffectors are involved in behavioral sensitization to amphetamine-induced stereotypy. In the present work, the effect of some of these drugs on sensitization was studied after intracortical administration in order to determine the role of the cortex in mediating their systemic effects. The dopamine antagonists sulpiride and spiperone were both ineffective against the acute response to amphetamine; nevertheless, both blocked the induction of sensitization, suggesting that the mesocortical dopamine pathway is not involved in the acute response but is necessary for the induction of sensitization. Both CPP, an NMDA receptor antagonist, and THIP, a GABA_A agonist, blocked the acute response and the induction of sensitization to amphetamine. On the other hand, mecamylamine, the nicotinic cholinergic antagonist, failed to affect either the acute response or the induction of sensitization, which suggests that the cortex is not a locus of its activity. Anisomycin, an inhibitor of protein synthesis, and diltiazem, a calcium-channel blocker, were both ineffective against the acute response, but both blocked induction. All of the drugs, except CPP and THIP, were ineffective against the expression of sensitization; therefore, the ability of the other drugs to block expression must reside within another locus. Bicuculline injected intracortically in non-convulsant doses produced a stereotypy indistinguishable from that induced by amphetamine; and the effect was readily antagonized by CPP administered either systemically or intracortically. In contrast, sulpiride by either route of administration failed to block the bicuculline-induced stereotypy; we conclude, therefore, that the stereotypic effect of bicuculline is not mediated by dopamine. These results imply that amphetamine-induced stereotypy is mediated in the cortex by the removal of the inhibitory control of the excitatory system. The data also suggest that cortical dopamine, as well as the NMDA and GABA_A systems, is important in sensitization to amphetamine. In general the data demonstrate that different neuroeffectors involved in sensitization exert their effects at different brain loci.     

The timing of the involvement of the frontal eye fields and posterior parietal cortex in visual search

The frontal eye fields (FEFs) and posterior parietal cortex (PPC) are important for target detection in conjunction visual search but the relative timings of their contribution have not been compared directly. We addressed this using temporally specific double pulse transcranial magnetic stimulation delivered at different times over FEFs and PPC during performance of a visual search task. Disruption of performance was earlier (0/40 ms) with FEF stimulation than with PPC stimulation (120/160 ms), revealing a clear and substantial temporal dissociation of the involvement of these two areas in conjunction visual search. We discuss these timings with reference to the respective roles of FEF and PPC in the modulation of extrastriate visual areas and selection of responses.