Prominent and persistent loss of past awareness in amnesia: delusion, impaired consciousness or coping strategy?

Profound loss of awareness for the past in amnesia has implications for our understanding of memory and belief systems, and how they may become disrupted in neurological conditions. We report the case of CW, a professional musician who became severely amnesic in 1985 following herpes simplex viral encephalitis (HSVE) at the age of 46 years. For many years CW stated several times a day that he had just woken up. He frequently wrote this in his diary too. When shown examples of his diary entries or videos of himself playing or conducting music, he recognised both his handwriting and himself on the video screen but stated vehemently that he "was not conscious then". In a previous paper (Wilson, Baddeley, & Kapur 1995), it was suggested that this lack of awareness for the past was a delusion, defined as a strongly held belief in the face of contradictory evidence (rather than implying any kind of psychiatric disorder per se). As a contribution to the academic debate regarding theories of "self", in the present paper we will review this explanation of CW's state as it had been in those early years, and we will also consider two other possibilities - namely, that CW had suffered from a loss of "autobiographical self" or "extended consciousness" (see Damasio, 2000, pp. 198-199), and that his verbal reports simply reflected a form of coping strategy to help him deal with the limited evidence he had available in "declarative" memory.     

Loss in risk-taking: absence of optimal gain or reduction in one's own resources?

Determining how living beings react to tasks that reflect realistic situations of risk has given rise to a vast literature. However, I argue that the methodologies traditionally used to test humans and nonhumans relative to risk often fail to achieve their goal. When risk is modelled in laboratory, potential decision cost (or potential loss) typically denotes an absence of optimal gain. In contrast, when risk occurs in real-life situations, potential loss denotes the reduction in an individual's limited resources - whether energetic, social, financial, etc. This conceptual difference about the nature of risk may have important implications for the understanding of the parameters that control risk-taking behaviour.     

Defective pantomime of object use in left brain damage: apraxia or asymbolia?

Disturbance of pantomime of object use in patients with left brain damage (LBD) and aphasia has been firmly established but its nature remains controversial. It may be due to an inability to perform movements from memory without external support by objects (apraxia) or to an inability to produce signs referring to absent objects and actions (asymbolia). The need to perform movements without external support is shared with imitation of gestures, and the demand to designate absent objects with drawing from memory. Both of these tasks have been found to be impaired in LBD. We examined pantomime of object use, drawing objects from memory, imitation of meaningless gestures, and aphasia in 40 patients with LBD and aphasia and compared them to healthy controls and to patients with right brain damage (RBD). Whereas drawing showed comparable sensitivity to LBD and RBD, pantomime was distinctly more disturbed in LBD than in RBD patients. Pantomime was worse than drawing in LBD but better than drawing in RBD. In the LBD group scores on pantomime showed significant correlations of very similar strength to drawing, imitation, and all language tests. Multidimensional scaling of the correlational structure placed pantomime in an intermediate position between verbal and non-verbal tests. We conclude that neither apraxia nor asymbolia can satisfactorily explain our results. It seems as if pantomime of object use taps a central aspect of left hemisphere function which is compromised by any LBD. We propose that this may be the ability to select and combine distinctive features of objects and actions.     

Ischemic preconditioning procedure induces behavioral deficits in the absence of brain injury?

Preconditioning describes a phenomenon whereby a sub-injury inducing insult can protect against a later larger injury. Thus, short-term cerebral ischemia can protect against a prolonged ischemia (ischemic preconditioning). This study examines rats undergoing ischemic preconditioning to test whether preconditioning may cause changes in behavior even though they do not cause an identifiable brain lesion. Rats had a transient (15 minutes) middle cerebral artery occlusion or a sham occlusion. Forelimb placing and forelimb use asymmetry tests were used to assess behavioral deficits. Brain histology, microglia activation, heat shock protein and ferritin levels were also examined. Ischemic preconditioning did not cause brain infarction, but induced behavioral changes. There were no significant differences between ischemic preconditioning and sham rats in the two behavioral tests at day one. However, the ischemic preconditioning group showed impaired forelimb placing at days 3, 7 and 14 (p<0.05). That group also had a significant (p<0.05) behavioral deficit in the forelimb use asymmetry test at days 3 and 7 (but not 14). Our present study demonstrated that a behavioral deficit occurred in ischemic preconditioning. This raises the question of whether induction of protective mechanisms by preconditioning stimuli necessarily involves some form of brain injury, detectable by changes in behavior though not by a lesion. This would be consistent with data suggesting that brain injury can initiate mechanisms potentially favorable to neuroplasticity and neuroprotection.     

Questioning the 'neuroprotective' hypothesis: does drug treatment prevent brain damage in early psychosis or schizophrenia?

The idea that psychotic disorders are characterised by progressive neurodegeneration that can be reversed by drug treatment is used to justify early treatment of increasing numbers of mostly young people. I argue that there is little evidence to support the view that old- or new-generation antipsychotics are 'neuroprotective', and some evidence that the drugs themselves may be responsible for the decline in brain matter observed in some studies.     

Are you listening? Brain activation associated with sustained nonspatial auditory attention in the presence and absence of stimulation

Neuroimaging studies investigating the voluntary (top‐down) control of attention largely agree that this process recruits several frontal and parietal brain regions. Since most studies used attention tasks requiring several higher‐order cognitive functions (e.g. working memory, semantic processing, temporal integration, spatial orienting) as well as different attentional mechanisms (attention shifting, distractor filtering), it is unclear what exactly the observed frontoparietal activations reflect. The present functional magnetic resonance imaging study investigated, within the same participants, signal changes in (1) a “Simple Attention” task in which participants attended to a single melody, (2) a “Selective Attention” task in which they simultaneously ignored another melody, and (3) a “Beep Monitoring” task in which participants listened in silence for a faint beep. Compared to resting conditions with identical stimulation, all tasks produced robust activation increases in auditory cortex, cross‐modal inhibition in visual and somatosensory cortex, and decreases in the default mode network, indicating that participants were indeed focusing their attention on the auditory domain. However, signal increases in frontal and parietal brain areas were only observed for tasks 1 and 2, but completely absent for task 3. These results lead to the following conclusions: under most conditions, frontoparietal activations are crucial for attention since they subserve higher‐order cognitive functions inherently related to attention. However, under circumstances that minimize other demands, nonspatial auditory attention in the absence of stimulation can be maintained without concurrent frontal or parietal activations. Hum Brain Mapp 35:2233–2252, 2014. © 2013 Wiley Periodicals, Inc.     

Mitochondrial damage and histotoxic hypoxia: a pathway of tissue injury in inflammatory brain disease?

The immunological mechanisms leading to tissue damage in inflammatory brain diseases are heterogeneous and complex. They may involve direct cytotoxicity of T lymphocytes, specific antibodies and activated effector cells, such as macrophages and microglia. Here we describe that in certain inflammatory brain lesions a pattern of tissue injury is present, which closely reflects that found in hypoxic conditions of the central nervous system. Certain inflammatory mediators, in particular reactive oxygen and nitrogen species, are able to mediate mitochondrial dysfunction, and we suggest that these inflammatory mediators, when excessively liberated, can result in a state of histotoxic hypoxia. This mechanism may play a major role in multiple sclerosis, not only explaining the lesions formed in a subtype of patients with acute and relapsing course, but also being involved in the formation of diffuse neurodegenerative lesions in chronic progressive forms of the disease.     

Intraoperative MRI in neurosurgery: technical overkill or the future of brain surgery?

The development of image-guided neurosurgery represents a substantial improvement in the microsurgical treatment of tumors, vascular malformations and other intracranial lesions. Despite the wide applicability and many fascinating aspects of image-guided navigation systems, a major drawback of this technology is they use images, mainly MRI pictures, acquired preoperatively, on which the planning of the operative procedure as well as its intraoperative performance is based. As dynamic changes of the intracranial contents regularly occur during the surgical procedure, the surgeon is faced with a continuously changing intraoperative field. Only intraoperatively acquired images will provide the neurosurgeon with the information he needs to perform real intraoperative image-guided surgery. A number of tools have been developed in recent years, like intraoperative ultrasound and dedicated moveable intraoperative CT units. Because of its excellent imaging qualities, combined with the avoidance of ionizing radiation, MRI currently is and definitely will be in the future for the superior imaging method for intraoperative image guidance. In this short overview, the development as well as some of the current and possible future applications of MRI-guided neurosurgery is outlined.     

Methylphenidate effects in the young brain: friend or foe?

Attention deficit hyperactivity disorder (ADHD) is one of the most prevalent neuropsychiatry disorders in children and adolescents, and methylphenidate (MPH) is a first-line stimulant drug available worldwide for its treatment. Despite the proven therapeutic efficacy, concerns have been raised regarding the possible consequences of chronic MPH exposure during childhood and adolescence. Disturbances in the neurodevelopment at these crucial stages are major concerns given the unknown future life consequences.This review is focused on the long-term adverse effects of MPH to the brain biochemistry. Reports conducted with young and/or adolescent animals and studies with humans are reviewed in the context of long-term consequences after early life-exposure. MPH pharmacokinetics is also reviewed as there are differences among laboratory animals and humans that may be relevant to extrapolate the findings.Studies reveal that exposure to MPH in laboratory animals during young and/or adolescent ages can impact the brain, but the outcomes are dependent on MPH dose, treatment period, and animal’s age. Importantly, the female sex is largely overlooked in both animal and human studies. Unfortunately, human reports that evaluate adults following adolescent or child exposure to MPH are very scarce. In general, human data indicates that MPH is generally safe, although it can promote several brain changes in early ages. Even so, there is a lack of long course patient evaluation to clearly establish whether MPH-induced changes are friendly or foe to the brain and more human studies are needed to assess the adult brain changes that arise from early MPH treatment.     

Does the cause of the mild traumatic brain injury affect the expectation of persistent postconcussion symptoms and psychological trauma?

Introduction: A controlled experiment of the effect of injury cause on expectations of outcome from mild traumatic brain injury (TBI) was conducted. Method: Ninety-three participants were randomly assigned to one of four conditions. The participants read a vignette that described a mild TBI (with fixed injury parameters) from a different cause (sport, domestic assault, fall, or motor vehicle accident). The effect of the manipulation on expectations of persistent postconcussion symptoms and psychological trauma was assessed with standard measures and a novel “threat-to-life” measure. Results: The Kruskal–Wallis H test for group differences revealed a significant but selective effect of group on symptom and trauma outcomes (?²s ≥ .10; large effects). Post hoc pairwise tests showed that, in most cases, there was an expectation of a worse outcome following mild TBI from a domestic assault than from the other causes (small-to-medium effects). Conclusion: Expectations were selectively altered by an experimental manipulation of injury cause. Given that expectations of outcome are known to affect mild TBI prognosis, the findings suggest the need for greater attention to injury cause.     

The problem of psychogenic symptoms: is the psychiatric community in denial?

Psychogenic symptoms are common and pose an uncomfortable challenge. Among psychogenic symptoms, psychogenic nonepileptic seizures (PNES) are common and have been extensively studied. They are unique in that, unlike most other psychogenic symptoms, they can be diagnosed with near certainty. PNES can be used as a model, as almost everything that applies to PNES applies to other psychogenic symptoms. According to DSM-IV, somatic symptoms are the main manifestation of three groups of disorders: somatoform disorders, factitious disorder, and malingering. Treatment is challenging. Unfortunately, psychogenic symptoms tend to be neglected. For example, the American Psychiatric Association has abundant written patient education material available on diverse topics, but none on somatoform disorders. Psychogenic symptoms are also not the subject of much clinical research. A search of the journal Neurology for 1994-2003 for the word psychogenic in the title found 21 articles, only 4 of which on topics other than psychogenic seizures. A similar search for original articles in the New England Journal of Medicine found no articles with psychogenic in the title and two with psychogenic in the abstract. Thus, there seems to be a severe disconnect between the frequency of the problem and the amount of attention devoted to it.     

Changes in the permeability of blood brain barrier and endothelial cell damage after cerebral ischemia

INTRODUCTION The relationship between the permeability of blood-brain barrier (BBB) and endothelial cells is very complex. In order to expound the effect of endothelial cells and its change mechanism in the change of permeability of BBB after cerebral isc…     

Is tau aggregation toxic or protective: a sensible question in the absence of sensitive methods?

In Alzheimer's disease brain, the microtubule-associated protein tau detaches from the microtubules, pathologically interacts with cellular proteins, and eventually forms insoluble aggregates that also bind and trap a myriad of proteins. As these proteins are depleted from the cellular pool, they are unavailable for physiological functions. Thus elevated tau levels are pathogenic, even in the absence of tau aggregation. Whereas it is reasonable to assume that tau aggregation is toxic during late stages of disease, the question arises whether early in disease it may be protective. This question can be addressed in tau transgenic animal models in which tau aggregation has been correlated with behavioral impairment. We discuss ways of how tau aggregation is monitored in these mice and what the detection limits are of these methods. We conclude that new tools are needed to measure the different stages of tau aggregation.     

Neural and humoral pathways of communication from the immune system to the brain: parallel or convergent?

The first studies carried out on the mechanisms by which peripheral immune stimuli signal the brain to induce fever, activation of the hypothalamic-pituitary-adrenal axis and sickness behavior emphasized the importance of fenestrated parts of the blood-brain barrier known as circumventricular organs for allowing blood-borne proinflammatory cytokines to act on brain functions. The discovery in the mid-1990s that subdiaphragmatic section of the vagus nerves attenuates the brain effects of systemic cytokines, together with the demonstration of an inducible brain cytokine compartment shifted the attention from circumventricular organs to neural pathways in the transmission of the immune message to the brain. Since then, neuroanatomical studies have confirmed the existence of a fast route of communication from the immune system to the brain via the vagus nerves. This neural pathway is complemented by a humoral pathway that involves cytokines produced at the level of the circumventricular organs and the choroid plexus and at the origin of a second wave of cytokines produced in the brain parenchyma. Depending on their source, these locally produced cytokines can either activate neurons that project to specific brain areas or diffuse by volume transmission into the brain parenchyma to reach their targets. Activation of neurons by cytokines can be direct or indirect, via prostaglandins. The way the neural pathway of transmission interacts with the humoral pathway remains to be elucidated.