The role of acetylcholine in negative encoding bias: Too much of a good thing?

Optimal acetylcholine (ACh) signaling is important for sustained attention and facilitates learning and memory. At the same time, human and animal studies have demonstrated increased levels of ACh in the brain during depressive episodes and increased symptoms of anxiety, depression, and reactivity to stress when ACh breakdown is impaired. While it is possible that the neuromodulatory roles of ACh in cognitive and affective processes are distinct, one possibility is that homeostatic levels of ACh signaling are necessary for appropriate learning, but overly high levels of cholinergic signaling promote encoding of stressful events, leading to the negative encoding bias that is a core symptom of depression. In this review, we outline this hypothesis and suggest potential neural pathways and underlying mechanisms that may support a role for ACh signaling in negative encoding bias.     

BDNF and epilepsy: too much of a good thing?

Various studies have shown that brain-derived neurotrophic factor (BDNF) increases neuronal excitability and is localized and upregulated in areas implicated in epileptogenesis. Seizure activity increases the expression of BDNF mRNA and protein, and recent studies have shown that interfering with BDNF signal transduction inhibits the development of the epileptic state in vivo. These results suggest that BDNF contributes to epileptogenesis. Further analysis of the cellular and molecular mechanisms by which BDNF influences excitability and connectivity in adult brain could provide novel concepts and targets for anticonvulsant or anti-epileptogenic therapy.     

Gastrostomy feeding in cerebral palsy: too much of a good thing?

Gastrostomy tube (GT) feeding in children with cerebral palsy (CP) is associated with significant increases in weight gain and, potentially, with overfeeding. This study aimed to measure energy balance and body composition in children with CP who were fed either orally or by GT. Forty children (27 males, 13 females; median age 8y 6mo; range 1y 4mo-18y 11mo) with spastic quadriplegic CP, of whom 22 were gastrostomy-fed and 18 orally-fed, underwent anthropometry, indirect calorimetry, and total energy expenditure determination (doubly-labelled water method). Total body water content (estimated by the 18O dilution method) was used to determine body composition. The Gross Motor Function Classification System (GMFCS) was used to determine the degree of motor impairment. GMFCS levels ranged from I to V; in the gastrostomy group 19 out of 22 were Level V and two out of 22 were Level IV. Within the orally-fed group, 11 out of 18 were Level V and four out of 18 were Level IV. Resting metabolic rate and total energy expenditure of the gastrostomy-fed children were lower but they had a significantly larger triceps skinfold thickness (p=0.01) and fat mass index (p=0.02) than the orally-fed children. Both groups had consistently higher body-fat content and lower fat-free (i.e. muscle and bone) content than the reference population of age- and sex-matched children without disabilities. This study has demonstrated the relatively low energy expenditure and high body-fat content of children with severe CP and highlighted the potential risk of overfeeding with available enteral feeds administered via GT.     

Diagnosis of asymptomatic natalizumab-associated PML: are we between a rock and a hard place?

The diagnosis of natalizumab-associated progressive multifocal leukoencephalopathy (PML) in multiple sclerosis patients in an asymptomatic stage is crucial since it is associated with better clinical outcome measures. Current diagnostic criteria on PML diagnosis in asymptomatic patients require the detection of JC virus and corresponding imaging findings. Magnetic resonance imaging (MRI) is the most sensitive diagnostic method for these purposes. However, the diagnosis of asymptomatic natalizumab-associated PML based on MRI findings can be challenging particularly in case of inconclusive or negative results on JC virus detection in the cerebrospinal fluid. In this report, we present a case series demonstrating different diagnostic scenarios of asymptomatic PML diagnosis based on MRI findings in combination with inconclusive or negative results on JC virus detection in the cerebrospinal fluid. We discuss the challenges of applying current PML diagnostic criteria in asymptomatic natalizumab-associated PML patients and stress the need for specific diagnostic criteria and guidelines regarding managing these diagnostic dilemmas in order to facilitate an early and correct diagnosis of PML presumably leading to a better clinical outcome.     

Dealing with highly active multiple sclerosis after natalizumab-associated PML: could rituximab be of help?

Neurological Sciences -     

Too Much of a Good Thing? Enhancement and the Burden of Self-Determination

There is a remedy available for many of our ailments: Psychopharmacology promises to alleviate unsatisfying memory, bad moods, and low self-esteem. Bioethicists have long discussed the ethical implications of enhancement interventions. However, they have not considered relevant evidence from psychology and economics. The growth in autonomy in many areas of life is publicized as progress for the individual. However, the broadening of areas at one’s disposal together with the increasing individualization of value systems leads to situations in which the range of options asks too much of the individual. I scrutinize whether increased self-determination and unbound possibilities are really in a person’s best interests. Evidence from psychology and economics challenges the assumption that unlimited autonomy is best in all cases. The responsibility for autonomous self-formation that comes with possibilities provided by neuro-enhancement developments can be a burden. To guarantee quality of life I suggest a balance of beneficence, support, and respect for autonomy.     

Too much thinking about thinking?: Metacognitive differences in obsessive-compulsive disorder

Negative appraisals of intrusive thoughts and beliefs about the importance of thoughts are considered core mechanisms in cognitive models of obsessive-compulsive disorder (OCD). In refinements of cognitive theory, differences in metacognitive processes have been emphasized. Cartwright-Hatton and Wells [J. Anxiety Disord. 37 (1997) 279-296] found that cognitive self-consciousness (CSC), a tendency to be aware of and monitor thinking, was the only metacognitive dimension that differentiated OCD patients from patients with generalized anxiety disorder. To evaluate the relative importance of different cognitive processes to OCD, we administered an expanded CSC scale and two state-of-the-art measures of thought appraisals and beliefs. Scores on the CSC scale reliably differentiated OCD patients (n=30), from an anxious comparison group (OAD, n=25) after controlling for scores on the two cognition measures. The tendency to excessively reflect upon one's cognitive processes may increase opportunities for negative appraisals of intrusive thoughts, foster over-importance of thought beliefs, and increase the likelihood of developing OCD.     

Is spinal cord isolation a good model of muscle disuse?

The patterns of normal daily activity that are required to maintain normal skeletal muscle properties remain unknown. The present study was designed to determine whether spinal cord isolation can be used as a reliable experimental model of neuromuscular inactivity, that is, as a baseline for the absence of activity. Electromyograms (EMGs) were recorded from selected hindlimb muscles of unanesthetized rats over 24-hour periods before and 7, 30, 60, and 90 days after surgical isolation of the lumbar spinal cord. Our data indicate that some rat slow muscle fibers pre-surgery were activated for less than 3 hours per day. Spinal cord isolation (SI) reduced the mean daily integrated EMG (IEMG) and daily EMG duration in the primary slow extensor muscle (soleus) to <1% of control, and in the primary fast extensor muscles [medial gastrocnemius (MG) and vastus lateralis (VL)] to <2% of control. These parameters were decreased to <8% and 3% of control, respectively, in a primary fast flexor muscle, the tibialis anterior (TA). From 30 to 90 days post-SI, the mean amplitudes of the spontaneous EMG bursts were relatively normal in the soleus, increased approximately 2-fold in the MG and VL, and increased approximately 4-fold in the TA. Some evidence of the normal antagonistic flexor-extensor relationship was apparent in the brief periods of recorded activity post-SI. These results indicate that SI eliminates nearly all of the normal EMG activity in the hindlimb muscles in the presence of relatively normal muscle innervation and functional intraspinal neural circuitry.     

How much food for a soul? Psychosomatic treatment of infantile feeding disorders

Severe feeding disorders often require inpatient treatment and need a holistic assessment and treatment approach. This article introduces some of the current literature concerning feeding disorders in infants and toddlers. The philosophy of the Department of Infant Psychosomatics at the University Children's Hospital Zürich emphasizes interdisciplinary teamwork, the application of psychodyamic tools in pediatric liaison psychiatry and utilization of group settings. Clinical approach and course of treatment are illustrated by three case reports, highlighting specific psychotherapeutic interventions with the parent-infant relationship in the context of a paediatric clinic.