Where do semantic errors come from?

We report the performance of two brain-damaged subjects (RGB and HW) whose frequent errors in spoken production are nearly always semantically related to the target word. Both subjects show similar, high rates of these "semantic" errors in oral naming and oral reading; yet neither subject makes semantic errors in comparable written tasks. Further, results of a variety of lexical tasks with the same stimuli demonstrate unimpaired comprehension of printed or spoken words, including those that are orally produced as semantic errors. These patterns of performance are interpreted as resulting from damage to the phonological output lexicon. The postulated deficit is contrasted to the hypothesis of impairment to the lexical-semantic component, required to explain performance by brain-damaged subjects described elsewhere who make seemingly identical types of oral production errors to those of RGB and HW, but, in addition, make comparable errors in writing and comprehension tasks.     

Where (in the brain) do semantic errors come from?

Background

Semantic errors result from the disruption of access either to semantics or to lexical representations. One way to determine the origins of these errors is to evaluate comprehension of words that elicit semantic errors in naming. We hypothesized that in acute stroke there are different brain regions where dysfunction results in semantic errors in both naming and comprehension versus those with semantic errors in oral naming alone.

Methods

A consecutive series of 196 patients with acute left hemispheric stroke who met inclusion criteria were evaluated with oral naming and spoken word/picture verification tasks and magnetic resonance imaging within 48 h of stroke onset. We evaluated the relationship between tissue dysfunction in 10 pre-specified Brodmann's areas (BA) and the production of coordinate semantic errors resulting from (1) semantic deficits or (2) lexical access deficits.

Results

Semantic errors arising from semantic deficits were most associated with tissue dysfunction/infarct of left BA 22. Semantic errors resulting from lexical access deficits were associated with hypoperfusion/infarct of left BA 37.

Conclusion

Our study shows that semantic errors arising from damage to distinct cognitive processes reflect dysfunction of different brain regions.     

Where do aphasic phonological errors come from? Evidence from phoneme movement errors in picture naming

This paper analyses the incidence and distribution of phonemic misordering errors (or ''contextual'' errors) in the phonologically related nonword responses of aphasic individuals. A diverse group of 22 individuals was examined in two separate picture naming studies. Contextual error rates were found to be above chance for only two of the participants. These participants had one unique feature: both were more accurate at word endings than word beginnings. Both also had a diagnosis of conduction aphasia and produced errors that were phonologically close to their targets, and at least one showed strong word length effects; however, none of these features was unique to them. The ''contextual'' individuals were not distinguishable from the other participants on the basis of: their production of formal paraphasias; their relative performance on word naming and repetition; or their performance on words relative to nonwords. The findings from this study are inconsistent with the notion that contextual errors result from a malfunction involving a dedicated postlexical phoneme sequencing stage. An alternative, single-stage account of phonological encoding is offered, in which differences in contextual error rates are attributed to individual variation in word production strategies.     

Delirium: Where do we stand?

Clinicians are likely to encounter delirium frequently, particularly in inpatient and intensive care settings. However, delirium is underrecognized and undertreated because of its heterogeneous and fluctuating presentation and due to the limitations in resources and training in contemporary clinical settings. Translation of current knowledge about delirium into clinical practice may improve patient care and benefit public health economics. Hence, this review comprehensively discusses the phenomenology and pathophysiology of delirium and its presenting features, risk factors, differential diagnoses, assessment, prognosis, and treatment with antipsychotics; the goal is to facilitate better prevention, recognition, and treatment of delirium. Available research is reviewed, limitations of the research are discussed, and future directions for further delirium research are identified.     

Primary care and mental health: Where do we go from here?

Primary care has been dubbed the “de facto” mental health system of the United States since the 1970s. Since then, various forms of mental health delivery models for primary care have proven effective in improving patient outcomes and satisfaction and reducing costs. Despite increases in collaborative care implementation and reimbursement, prevalence rates of major depression in the United States remain unchanged while anxiety and suicide rates continue to climb. Meanwhile, primary care task forces in countries like the United Kingdom and Canada are recommending against depression screening in primary care altogether, citing lack of trials demonstrating improved outcomes in screened vs unscreened patients when the same treatment is available, high false-positive results, and small treatment effects. In this perspective, a primary care physician and two psychiatrists address the question of why we are not making headway in treating common mental health conditions in primary care. In addition, we propose systemic changes to improve the dissemination of mental health treatment in primary care.     

SUDEP counseling: Where do we stand?

Sudden unexpected death in epilepsy (SUDEP) is the leading cause of epilepsy-related death in children and adults living with epilepsy. Several recent clinical practice guidelines have recommended that all individuals living with epilepsy and their caregivers be informed about SUDEP as a part of routine epilepsy counseling. Furthermore, several studies over the last two decades have explored the state of SUDEP counseling. Patients with epilepsy and their families want to be informed about the risk of SUDEP at or near the time of diagnosis, and preferably in person. Despite guideline recommendations, many pediatric and adult neurologists do not routinely inform individuals with epilepsy and their families about SUDEP. Some neurologists discuss SUDEP with only a subset of patients with epilepsy, such as those with risk factors like frequent generalized or focal to bilateral tonic–clonic seizures, nocturnal seizures, noncompliance, or medically refractory epilepsy. Proponents of routine SUDEP counseling argue that patients with epilepsy and their families have a “right to know” and that counseling may positively impact epilepsy self-management (i.e., behavioral modification and risk reduction). Some neurologists still believe that SUDEP counseling may cause unnecessary stress and anxiety for patients and their families (although this is erroneous) and that they also have a “right not to know.” This narrative review explores the current gaps in SUDEP counseling, patients' and caregivers' perspectives of SUDEP counseling, and SUDEP prevention.     

Lateral line receptors: where do they come from developmentally and where is our research going?

The lateral line system is composed of both mechanoreceptors, which exhibit little variation in structure between taxonomic groups, and electroreceptors, which exhibit considerably more variation. Cathodally sensitive ampullary electroreceptors are the primitive condition and are found in agnathans, chondrichthyans, and most osteichthyans. Aquatic amphibians also have ampullary electroreceptors for at least part of their life cycle. The more recently evolved anodally sensitive ampullary electroreceptors and tuberous electroreceptors are only found in four groups of teleost fishes. The basic ontogenetic unit of lateral line development is the dorsolateral placode. Primitively, there are six pairs of placodes, which pass through sequential stages of development into lateral line receptors. There is no question about the origin of primitive mechanoreceptors or electroreceptors, however, we do not have a good understanding of the origin of teleost mechanoreceptors and their ampullary or tuberous electroreceptors; do they come exclusively from dorsolateral placodes or from neural crest or even general ectoderm? A second intriguing lateral line question is how certain teleost fish groups evolved tuberous electroreceptors. Electroreception appears to have re-evolved at least twice in teleosts after being lost during the neopterygian radiation. It has been suggested that the development of tuberous electroreceptors might be due to changes in placodal patterning or a change in the general ectoderm that placodes arise from. Unfortunately, our understanding of lateral line origins in fishes is very sketchy, and, if we are to answer such an evolutionary question, we first need more complete information about lateral line development in a variety of fishes, which can then be combined with gene expression data to better interpret lateral line receptor development.     

Anemia and stroke: Where do we stand?

Anemia seems to have a clear relationship with cerebrovascular events (CVEs), as there is a direct connection between central nervous system, blood supply, and tissue oxygen delivery. Anemia is considered a hyperkinetic state which disturbs endothelial adhesion molecule genes that may lead to thrombus formation. Furthermore, blood flow augmentation and turbulence may result in the migration of this thrombus, thus producing artery‐to‐artery embolism. It is for this reason that anemia is characterized as “the fifth cardiovascular risk factor.” Anemia is consistently present in patients with acute stroke, ranging from 15% to 29%, while the mortality rate was significantly higher in patients suffering from anemia at the time of admission. Different types of anemia (sickle cell disease, beta thalassemia, iron deficiency anemia [IDA]) have been associated with increased cardiovascular and CVE risk. The relation between hemoglobin level and stroke would require further investigation. Unfortunately, treatment of anemia in cardiovascular and cerebrovascular disease still lacks clear targets and specific therapy has not developed. However, packed red blood cell transfusion is generally reserved for therapy in patients with CVEs. What is more, treatment of IDA prevents thrombosis and the occurrence of stroke; although iron levels should be checked, chronic administration favors thrombosis. Regarding erythropoietin (EPO), as there is lack of studies in anemic stroke patients, it would be desirable to utilize both neuroprotective and hematopoietic properties of EPO in anemic stroke patients. This review aims to clarify the poorly investigated and defined issues concerning the relation of anemia and CVEs.     

Functional significance of the rapid regulation of brain estrogen action: where do the estrogens come from?

Estrogens exert a wide variety of actions on reproductive and non-reproductive functions. These effects are mediated by slow and long lasting genomic as well as rapid and transient non-genomic mechanisms. Besides the host of studies demonstrating the role of genomic actions at the physiological and behavioral level, mounting evidence highlights the functional significance of non-genomic effects. However, the source of the rapid changes in estrogen availability that are necessary to sustain their fast actions is rarely questioned. For example, the rise of plasma estrogens at pro-estrus that represents one of the fastest documented changes in plasma estrogen concentration appears too slow to explain these actions. Alternatively, estrogen can be synthesized in the brain by the enzyme aromatase providing a source of locally high concentrations of the steroid. Furthermore, recent studies demonstrate that brain aromatase can be rapidly modulated by afferent inputs, including glutamatergic afferents. A role for rapid changes in estrogen production in the central nervous system is supported by experiments showing that acute aromatase inhibition affects nociception as well as male sexual behavior and that preoptic aromatase activity is rapidly (within min) modulated following mating. Such mechanisms thus fulfill the gap existing between the fast actions of estrogen and their mode of production and open new avenues for the understanding of estrogenic effects on the brain.     

Spinal Muscular Atrophy Therapeutics: Where do we Stand?

Spinal muscular atrophy (SMA) is an inherited neuromuscular disorder pathologically characterized by the degeneration of motor neurons in the spinal cord and muscle atrophy. Motor neuron loss often results in severe muscle weakness causing affected infants to die before reaching 2 years of age. Patients with milder forms of SMA exhibit slowly progressive muscle weakness over many years. SMA is caused by the loss of SMN1 and the retention of at least 1 copy of a highly homologous SMN2. An alternative splicing event in the pre-mRNA arising from SMN2 results in the production of low levels of functional SMN protein. To date, there are no effective treatments available to treat patients with SMA. However, over the last 2 decades, the development of SMA mouse models and the identification of therapeutic targets have resulted in a promising drug pipeline for SMA. Here, we highlight some of the therapeutic strategies that have been developed to activate SMN2 expression, modulate splicing of the SMN2 pre-mRNA, or replace SMN1 by gene therapy. After 2 decades of translational research, we now stand within reach of a treatment for SMA.

Electronic supplementary material

The online version of this article (doi:10.1007/s13311-015-0337-y) contains supplementary material, which is available to authorized users.     

Trophic factors for Parkinson's disease: Where are we and where do we go from here?

Perhaps the most important unmet clinical need in Parkinson's disease (PD) is the development of a therapy that can slow or halt disease progression. Extensive preclinical research has provided evidence for the neurorestorative properties of several growth factors, yet only a few have been evaluated in clinical studies. Attempts to achieve neuroprotection by addressing cell‐autonomous mechanisms and targeting dopaminergic neurons have been disappointing. Four different trophic factors have so far entered clinical trials in PD: glial cell line‐derived growth factor, its close structural and functional analog neurturin, platelet‐derived growth factor and cerebral dopaminergic neurotrophic factor. This article reviews the pre‐clinical evidence for the neuroprotective and neurorestorative actions of these growth factors and discusses limitations of preclinical models, which may hamper successful translation to the clinic. We summarize the previous and ongoing clinical trials using growth factors in PD and emphasize the caveats in clinical trial design that may prevent the further development and registration of potentially neuroprotective and neurorestorative treatments for individuals suffering from PD.     

Are drawing perseverations part of the neglect syndrome?

Unilateral neglect patients typically omit to cancel contralesional targets. Moreover, they can repeatedly cancel ipsilesional stimuli exhibiting what is termed ‘perseverative behavior’. Two alternative accounts of this behavior have been proposed. According to one of them, it is considered as integral to neglect and due either to a perceptual (allochiria), or a premotor (directional hypokinesia) pathological mechanism leading to the ipsilesional displacement of contralesional responses. According to the other one, perseverations are interpreted as the consequence of motor-control-disinhibition co-occurring with, although independent of, spatial neglect. We compared some crucial predictions of these two hypotheses on a group of 10 right-brain-damaged patients, eight with neglect and two without neglect, showing a perseverative behavior in both conventional and experimental cancellation tasks. In our experiment, the spatial location and the numerosity of targets were manipulated to obtain different degrees of horizontal alignment between targets on the left and on the right of the central vertical axis of the sheet. We found that ipsilesional perseverations were not influenced by left neglected targets and were not correlated to neglect severity. Additionally, perseverative errors were associated with right basal ganglia lesions rather than with presence of neglect. These findings support the view that two different pathological mechanisms might be involved in left spatial neglect and ipsilesional perseverative behavior.     

Public Understandings of Addiction: Where do Neurobiological Explanations Fit?

Developments in the field of neuroscience, according to its proponents, offer the prospect of an enhanced understanding and treatment of addicted persons. Consequently, its advocates consider that improving public understanding of addiction neuroscience is a desirable aim. Those critical of neuroscientific approaches, however, charge that it is a totalising, reductive perspective–one that ignores other known causes in favour of neurobiological explanations. Sociologist Nikolas Rose has argued that neuroscience, and its associated technologies, are coming to dominate cultural models to the extent that 'we' increasingly understand ourselves as 'neurochemical selves'. Drawing on 55 qualitative interviews conducted with members of the Australian public residing in the Greater Brisbane area, we challenge both the 'expectational discourses' of neuroscientists and the criticisms of its detractors. Members of the public accepted multiple perspectives on the causes of addiction, including some elements of neurobiological explanations. Their discussions of addiction drew upon a broad range of philosophical, sociological, anthropological, psychological and neurobiological vocabularies, suggesting that they synthesised newer technical understandings, such as that offered by neuroscience, with older ones. Holding conceptual models that acknowledge the complexity of addiction aetiology into which new information is incorporated suggests that the impact of neuroscientific discourse in directing the public's beliefs about addiction is likely to be more limited than proponents or opponents of neuroscience expect.     

Where do families of children with epilepsy obtain their information?

A structured interview of 84 families of children with epilepsy followed through the neurology clinic of a tertiary care children's hospital was conducted to assess the epilepsy-specific information sources accessed and the perceived accuracy of these sources. Families accessed a mean of 3.5 sources from or specifically recommended by the clinic or family doctor and 4.1 sources outside these areas. Families of children with intractable epilepsy and higher-educated parents, but not those of higher socioeconomic status, consulted more extensively. The perceived accuracy of information rated highest for clinic-recommended Internet sites (100%), the clinic nurse (97%), and the neurologist (93%). Sources external to the clinic had variable ratings; those with the greatest perceived accuracy included other Internet sites or family members within the medical profession (85% for both) and lay organizations (84%). Friends within the medical profession, other families, and complementary health care providers also ranked highly. Recommendation of sites and books by epilepsy clinics is more helpful than general handouts.