SCIWORA in MRI era

The aim of this report is to discuss the use of the term ‘Spinal Cord Injury Without Radiographic Abnormality’ (SCIWORA) in the medical literature ever since MRI became commonly employed in the diagnosis of spinal cord injuries. Using the PubMed database and the keywords ‘SCIWORA and MRI’, we found 30 published articles in the English-language literature. Incidence, clinical and radiological data, and MRI findings were evaluated in all articles, which included one meta-analysis, two reviews, 10 case series, and 17 case reports. The incidence of SCIWORA among children was found to be between 3.3% and 32.0%. This wide range was directly related to patients’ age, authors’ specialty, and utilization of MRI. After MRI became commonly used for spinal injuries, the term has taken on an ambiguous meaning in the literature. In our opinion, if any pathology is detected on MRI with or without radiographic abnormality, the patients should not be classed, as SCIWORA and ‘real-SCIWORA’ should be determined as ‘Spinal Cord Injury Without Neuroimaging Abnormality’ in cases with normal MRI.     

Neuronotrophic factors and their antibodies: In vitro microassays for titration and screening

Using nerve growth factor (NGF), anti-NGF sera and dissociated neonatal mouse dorsal root ganglionic neurons we present a microculture assay methodology for (1) the titration of neuronotrophic factor (NTF) activity in monolayer culture, (2) the titration of NTF antibodies which ‘block’ NTF biological activity, (3) the titration of NTF antibodies that bind and remove (sequester) NTF from culture medium and (4) a large-scale, convenient, and rapid screening for NTF biological activity as well as for NTF ‘blocking’ or ‘sequestering’ antibodies. These quantitative and qualitative in vitro microimmunoassays should be applicable to any neuronotrophic factor or its antibody, even when the agent is only available in crude, unpurified form. Since the microculture systems permit the simultaneous screening of one thousand samples per day they should be useful for the detection and quantitation of monoclonal antibodies present in hybridoma-conditioned media.     

Axonal transport and tissue contents of substance P in rats with long-term streptozotocin-diabetes. Effects of the aldose reductase inhibitor ‘statil’

This study examined the axonal transport of substance P-like immunoreactivity (SPLI) and its content in dorsal root ganglion, trigeminal ganglion, stomach and ileum of non-diabetic rats and two groups of rats with streptozotocin-induced diabetes of 9 months duration. One diabetic group received the aldose reductase inhibitor ‘Statil’ throughout the period of study. To reduce morbidity all diabetic animals were given twice-weekly injections of a long-acting insulin which restricted weight loss but did not prevent regular and severe hyperglycaemia. Axonal transport of SPLI was studied by measurement of accumulation at 12 h ligatures on the left sciatic nerve. There were no differences between the 3 groups either in the calculated anterograde and retrograde mean rates of accumulation (ranges 6.0 to 7.6 and 0.38 to 0.72 mm/h respectively) or mobile fractions of SPLI (means from 0.54 to 0.58). There were, however, marked reductions in anterograde and retrograde accumulations of SPLI in the constricted nerves of the ‘untreated’ diabetics (respectively 57 and 33% of controls;P < 0.01 for both). In the ‘Statil’-treated rats these deficits were attenuated (80 and 75% of controls). Diabetes also reduced the SPLI content of unligated sciatic nerve and trigeminal ganglion (65 and 75% of controls). ‘Statil’ prevented the deficit in the ganglion, but not in the nerve. ‘Statil’ treatment prevented themyo-inositol depletion and attenuated the sorbitol and fructose accumulation seen in the sciatic nerves of the untreated diabetic animals suggesting effective inhibition of aldose reductase in this tissue. The total SPLI content of the stomach and 1-cm segments of ileum were unaltered in the diabetic animals but due to the increased weights of these tissues the SPLI content per unit weight was reduced. These changes were unaffected by ‘Statil’.     

Visual receptive fields of single cells in the pigeon's optic tectum

Three hundred and ninety-four units within the optic tectum of pigeons were studied using extracellular recording. According to their receptive field properties, they were classified in 4 major classes. (1) Concentrically organized fields (6%), composed of a center ‘on’ and an antagonistic surround ‘off’, or the reverse. The center and the surround had identical spectral sensitivities. Motion of a white or black spot across the center-surround evoked equally strong responses for all directions of movement. (2) Cells with homogeneous ‘on’ or ‘off’ fields (1.3%) respond well to flashes of light, but have no antagonistic surround. (3) Movement selective cells (72%) respond preferentially to moving stimuli, and poorly or not at all to static spots. According to the size of their receptive fields these were classified as ‘small’ (2°), ‘middle’ (5°) and ‘large field’ (31°). Cells with ‘large fields’ were always found at the deepest part of the electrode penetration (1100 μm to 1400 μm). (4) Directionally selective cells (21%) respond optimally to motion of the spot in one direction ‘preferred’ and not to movement in the opposite direction ‘null’. They were always recorded in the superficial range of penetration, above 1000 μm. Although the cells in the pigeon's optic tectum seem to be preferentially stimulated by moving objects, directional selectivity appears to be a characteristic of the superficial tectal layers. These results, together with other studies, suggest that the ‘output’ of the pigeon's tectum might carry directionally coded signals.     

The assessment of alexithymia: A critical review of the literature and a psychometric study of the Toronto Alexithymia Scale-20

Objective: The objectives were to give an overview of studies on the validity of the Toronto Alexithymia Scale (TAS-20) and to present data regarding the validity of the TAS-20. Methods: The literature on the psychometric properties of the TAS-20 was reviewed and a study was conducted of its psychometric properties in a sample of students and a sample of psychiatric outpatients using a statistical method allowing identification of a stable factor structure. Results: The review revealed that the majority of studies on the TAS-20 were conducted with nonpatient samples. The factorial validity and reliability of the dimensions ‘identifying feelings’ (DIF) and ‘describing feelings’ (DDF) could be replicated in many of these studies. However, in practically all studies the dimension ‘externally oriented thinking’ (EOT) appears to be unreliable. In addition, the presupposed fantasy aspect of the alexithymia construct is not included in the TAS-20. Although many studies were conducted on the construct validity of the TAS-20, no studies have been published on its criterion validity. Some studies show a different factor structure to exist in patient samples. This was confirmed in our own study in which the dimensions ‘identifying feelings’ and ‘describing feelings’ collapsed into one single subscale. As in other studies, the reliability of the dimension ‘EOT’ was low. Conclusion: The TAS-20 has some important shortcomings with respect to validity and reliability. For the assessment of alexithymia in empirical research, it is recommended to use the TAS-20 in combination with other instruments. We do not recommend the TAS-20 to be used in clinical practice.     

The case for episodic memory in animals

The conscious recollection of unique personal experiences in terms of their details (what), their locale (where) and temporal occurrence (when) is known as episodic memory and is thought to require a ‘self-concept’, autonoetic awareness/conciousness, and the ability to subjectively sense time. It has long been held that episodic memory is unique to humans, because it was accepted that animals lack a ‘self-concept’, ‘autonoetic awareness’, and the ability to ‘subjectively sense time’. These assumptions are now being questioned by behavioral evidence showing that various animal species indeed show behavioral manifestations of different features of episodic memory such as, e.g. ‘metacognition’, ‘conscious recollection’ of past events, ‘temporal order memory’, ‘mental time travel’ and have the capacity to remember personal experiences in terms of what happened, where and when. The aim of this review is to provide a comprehensive overview on the current progress in attempts to model different prerequisites and features of human episodic memory in animals and to identify possible neural substrates of animal episodic memory. The literature covered includes behavioral and physiological studies performed with different animal species, such as non-human primates, rodents, dolphins and birds. The search for episodic memory in animals has forced researchers to define objective behavioral criteria by which different features of episodic memory can be operationalized experimentally and assessed in both animals and humans. This is especially important because the current definition of episodic memory in terms of mentalistic constructs such as ‘self’, ‘autonoetic awareness/consciousness’, and ‘subjectively sensed time’, not only hinders animal research on the neurobiology of episodic memory but also research with healthy human subjects as well as neuropsychiatric patients with impaired language or in children with less-developed verbal abilities.     

Headache and the greater occipital nerve

This paper examines the clinical features of 500 patients with idiopathic headache. Of the 383 patients diagnosed as migraine, it was found that 184 (48%) were suffering from headaches due to irritation of the greater occipital nerve (GON). Such headaches could be arrested by injecting the ipsilateral greater occipital nerve (GON) with local anaesthetic, prevented for up to 4 weeks by injecting ‘Depomedrol’ into the region of the nerve and for several months by surgical division of the nerve. It is suggested that such patients are not suffering from typical migraine but from headaches due to neural irritation, which, for want of a better name, have been called ‘occipital neuralgia’.     

Convolution of mini distributions for fitting evoked synaptic amplitude histograms

According to a basic formulation of the quantal model, evoked synaptic currents are made up of a linear summation of uniquantal synaptic currents, which in turn are equivalent to the spontaneous miniature synaptic currents (‘minis’) that often persist when evoked neurotransmitter release is blocked. Here I describe a convolution method for calculating linear summations of the ‘mini’ amplitude distribution, which can then be fitted to the measured amplitude distribution for evoked synaptic currents. Provided certain conditions are satisfied, this method can give information about the statistics of neurotransmitter release even when clear quantal peaks are not apparent in the evoked amplitude distribution. The method is illustrated by an experiment in which the appropriate minis are identified with the asynchronous excitatory postsynaptic currents that follow synaptic stimulation when the cell is bathed in strontium. Finally, I discuss the assumptions behind the convolution method, and the conditions under which the properties of the minis are likely to be appropriate for an analysis of this type.     

Long‐term walking ability and patient satisfaction after lower limb functional surgery in patients affected by Charcot‐Marie‐Tooth disease: A retrospective study

Structural foot deformities consequent to Charcot Marie Tooth (CMT) can be treated by functional surgery (FS). This study aims to evaluate both long‐term walking ability and patients' satisfaction in CMT subjects who underwent FS during their lifetime. We conducted a retrospective observational study. Age, sex, CMT type, comprehensive surgical history, current walking ability assessed by the Walking Handicap Scale (WHS) and patients' global impression of change (pGIC) were retrieved from a custom database managed at our institution. WHS and pGIC were assessed between mid‐2018 and mid‐2019. Data from 79 patients were screened and 63 were included, 35W‐28M, mean age 42 (15), with demyelinating (75%), axonal (20%), and other types (5%) of CMT, who underwent FS between 1967 and 2018. FS evolved significantly over the years from bone‐related procedures (e.g., arthrodesis) to both bone and soft tissues‐related procedures. The re‐intervention rate decreased from 70% before 2000 to 32% in the last decade. Complications arose in five cases. FS was mainly performed on adults (73%). WHS was ≥ 5 in three‐quarters of the sample (range 1‐6) and was significantly affected by age groups in patients with demyelinating CMT (n=47, p<0.01, non‐parametric ANOVA). Nearly 80% of patients were satisfied with FS (pGIC ≥ 4). In conclusion, CMT subjects who underwent FS surgery maintained a high gait efficiency in the long‐term period, with middle to high levels of satisfaction in the majority of the cases. This confirms the validity of FS in the management of acquired foot deformities in CMT patients.     

Dopamine dependency of cognitive switching and response repetition effects in Parkinson's patients

A group of people with Parkinson's disease and a group of matched controls were tested on a task involving a switch between perceptual dimensions. Patients were tested both ‘on’ and ‘off’ their normal medication cycles. Stimuli appeared in pairs for each trial, with each stimulus consisting of a color and a shape. One dimension of color and one of shape were mapped to each of two response keys. A cue was presented concurrently with each stimulus to indicate whether to respond on the basis of color or shape, following procedures developed by Hayes et al. [Hayes, A.E., Davidson, M.C., Keele, S.W., & Rafal, R.D. (1998). Toward a functional analysis of the basal ganglia.Journal of Cognitive Neuroscience, 10, 178–198]. Replicating previous literature, abnormally large switch costs were observed in patients who were off their normal medication cycles. A novel finding was that patients in the ‘on’ state demonstrated a slight reversal of switch costs. Also novel, reaction time (RT) costs associated with switching between response keys, and interactions between response switching and task switching were influenced predominantly by on–off dopamine manipulations. It is concluded that abnormal task switching costs and response repetition effects likely reflect impairments of activation and inhibition, and both effects are dopamine-dependent.     

Coping with critical life events and lack of control--the exertion of control

Coping strategies in relation to unfair treatment or conflicts at work are discussed. ‘Covert coping’ has been assessed by means of a short questionnaire. Its relationship with cardiovascular risk and sick leave has been examined in an epidemiological study (WOLF) of working men and women in Stockholm. The findings indicate that in men ‘covert coping’ is associated with elevated cardiovascular risk and prospective long-term sick leave. In women such a coping strategy is related to current sick leave, but not to cardiovascular risk or long-term sick leave. Openness of coping strategies is also discussed in relation to bouts of anger preceding myocardial infarction. Another epidemiological study (SHEEP, ONSET) has shown that severe bouts of anger are reported significantly more often than expected during the hour preceding myocardial infarction. This was not the case in subjects who reported ‘open coping patterns’, however. Openness of coping strategies is partly determined by the working climate—the higher the decision latitude, the less ‘covert’ the coping strategies. The results support the idea that dialogue in the work place may be health promoting.     

Integration of synaptic and intrinsic dendritic currents in cat spinal motoneurons

The results of recent studies designed to reveal some of the ‘rules’ governing the integration of synaptic and intrinsic dendritic currents in spinal motoneurons are reviewed. When two or more sources of synaptic input are activated concurrently, their combined postsynaptic effects on cat spinal motoneurons with ‘passive dendrites’ are generally equal to or slightly less than those predicted from the linear sum of their individual effects. However, for experimental preparations in which active conductances on motoneuron dendrites are enabled, instances of greater-than- or less-than linear summation can occur. Further, these studies demonstrate that the persistent inward currents that are generated by motoneuron dendrites provide an intrinsic source of excitatory drive that is larger than those associated with any of the individual synaptic input systems studied to date. Since these intrinsic depolarizing currents can be rapidly inactivated by a hyperpolarizing input, they are ideally suited to providing a major source of the alternating ‘drive’ to motoneurons during locomotion.     

The effects of chronic continuous versus intermittent levodopa treatments on striatal and extrastriatal D1 and D2 dopamine receptors and dopamine uptake sites in the 6-hydroxydopamine lesioned rat — an autoradiographic study

The effects of chronic ‘continuous’ infusion and ‘intermittent’ modes of levodopa/carbidopa administration on apomorphine induced circling behaviour, DA uptake sites (labelled with [³H]mazindol) and D₁ and D₂ DA receptor binding (labelled with [³H]SCH 23390 and [³H]sulpiride, respectively) were investigated in rats with unilateral 6-OHDA lesions of the medial forebrain bundle. The circling behaviour in response to apomorphine was greatly enhanced following chronic ‘intermittent’ but not ‘continuous’ levodopa treatments. Following the ‘intermittent’ regime, the lower dose of apomorphine induced a period of intense circling with delayed onset and rapid offset, than in rats given either ‘continuous’ infusion of levodopa or saline. The 6-OHDA lesion itself induced gross depletion of [³H]mazindol binding in all striatal subregions, NAc and OT, but not frontal cortex. [³H]Sulpiride binding in the ventrolateral striatal quadrant was increased on the denervated side and this correlated with the peak contralateral turns in response to 0.5 mg/kg apomorphine challenge. This asymmetry in striatal [³H]sulpiride binding was reduced in both groups of rats receiving levodopa. [³H]sulpiride binding in the NAc and OT and [³H]SCH 23390 binding in the striatum, NAc, OT and SNr were unaffected by DA denervation or either regime of levodopa treatments. ‘Continuous’ infusion and not ‘intermittent’ injections of levodopa reduced [³H]mazindol binding in the striatal subregions and the frontal cortex on both the denervated and intact sides. The potentiation of the behavioural response to apomorphine by chronic ‘intermittent’ levodopa treatment does not correspond with the levodopa induced alterations in striatal or extrastriatal DA receptors. In the same group of animals the narrowing of the duration of response to the lower dose of apomorphine may mimic the fluctuations in response to levodopa, seen clinically in long-term levodopa treated parkinsonian patients.     

ERP 'old/new' effects: memory strength and decisional factor(s)

Event-related potentials (ERPs) were recorded while subjects made old/new recognition judgments on new unstudied words and old words which had been presented at study either once (‘weak’) or three times (‘strong’). The probability of an ‘old’ response was significantly higher for strong than weak words and significantly higher for weak than new words. Comparisons were made initially between ERPs to new, weak and strong words, and subsequently between ERPs associated with six strength-by-response conditions. The N400 component was found to be modulated by memory trace strength in a graded manner. Its amplitude was most negative in new word ERPs and most positive in strong word ERPs. This ‘N400 strength effect’ was largest at the left parietal electrode (in ear-referenced ERPs). The amplitude of the late positive complex (LPC) effect was sensitive to decision accuracy (and perhaps confidence). Its amplitude was larger in ERPs evoked by words attracting correct versus incorrect recognition decisions. The LPC effect had a left>right, centro-parietal scalp topography (in ear-referenced ERPs). Hence, whereas, the majority of previous ERP studies of episodic recognition have interpreted results from the perspective of dual-process models, we provide alternative interpretations of N400 and LPC old/new effects in terms of memory strength and decisional factor(s).     

Two types of phonological dyslexia - a contemporary review

Friedman (1995) presents a review of 6 phonological dyslexic cases in which she suggests that this reading impairment is divisible into subtypes on the basis of two straightforward behavioural profiles: (1) cases with poor function word reading and normal nonword repetition (3 cases) and (2) cases with good function word reading and poor nonword repetition (3 cases). This evidence is interpreted as support for a reading model that does not posit a non-lexical reading route (Harm and Seidenberg, 2001, 2004; Plaut, et al. 1996), with the pattern of impairment in case (1) being due to disruption of direct connections between orthography–phonology and in case (2) being due to a ‘generalised’ impairment of phonology. The current review re-evaluates the validity of Friedman's original criteria as a basis for identifying ‘subtypes’ of phonological dyslexia with a larger sample of 38 documented cases. On balance it is found that the majority does not easily fit either subtype on the basis of the expected behavioural profiles. Thus the present survey would suggest that Friedman's criteria for classification of phonological dyslexia is not particularly useful for the general population of such cases. However, subsequent correlational analyses did find evidence in support of a relationship between nonword reading impairment and nonword repetition/function word reading impairment. This finding is largely consistent with the principles of the type of reading model outlined by Friedman (1995), although other potential accounts cannot be ruled out. These findings are discussed in greater detail with relation to present models of reading and potential avenues for further research are proposed.     

Changes in event-related potentials in a three-stimulus auditory oddball task after mild head injury

Previous research has demonstrated changes in event-related potentials in a variety of cognitive tasks after severe closed head injury. We sought to establish if similar changes were present in patients who had sustained only apparently mild head injury (MHI) by recording event-related potentials in a group of 24 mild head injured and 24 control participants during a three-stimulus auditory target detection task. For this ‘oddball’ task participants were required to press a button every time they heard a rare target tone and to ignore rare novel sounds and frequent non-target tones. Neuropsychological test results indicated that the mild head injured group had mild memory and attention impairments. Analysis of behavioural performance on the three-stimulus ‘oddball’ task showed no difference in reaction times or error rates between the two groups. Target condition N2 deflections appeared to be larger in the mild head injured but peak amplitude measures revealed that this effect was not significant. There were no significant differences in the amplitude or latency of the P3b evoked by target stimuli or the P3a evoked by novel stimuli. However, a putative ‘O-wave’ or ‘reorienting negativity’ following the P3a was more negative in the mild head injured group suggesting increased activation of components of the attention network. These findings lend support to the hypothesis that MHI can cause subtle cognitive impairments that are associated with abnormal allocation of attention resources in the context of normal behavioural performance.     

Refining the diagnoses of inattention and overactivity syndromes: A reanalysis of the Multimodal Treatment study of attention deficit hyperactivity disorder (ADHD) based on ICD-10 criteria for hyperkinetic disorder

There are large differences between nations in the diagnosis and management of children with marked impulsiveness and inattention. The differences extend to the names and definitions of disorder and the extent to which medication should be used. This paper uses data from a large randomized clinical trial of pharmacological and psychosocial treatments, conducted in North America, to clarify its implications for other parts of the world. A diagnostic algorithm was applied to 579 children, diagnosed with ADHD-Combined Type in the MTA trial, to generate the ICD-10 diagnosis of ‘hyperkinetic disorder’ (HD); only a quarter met these more stringent criteria. HD was a moderator of treatment response. The superiority of medication to behavioral treatment was greater for children with HD. Children with ADHD but not HD also showed some improvement with medication. The results provide evidence for the validity of HD as a subgroup of those presenting ADHD; and suggest that treatment with stimulants is a high priority in children with HD. Results also suggest that some children with other forms of ADHD will respond better to medication than to psychosocial intervention, and therefore that European guidelines should extend their indications.     

A reweighting of receptor mechanisms in the ground squirrel retina: PIII and B-wave spectral sensitivity functions

PIII and b-wave spectral sensitivity functions were measured under various adapted conditions in the 13-lined ground squirrel. The PIII was isolated by intravitreal injection of sodium l-aspartate. Under the conditions studied, the PIII spectral sensitivity function always fitted the absorption spectrum of a 518 ± 3 nm Dartnall nomogram. This suggests that of the three photoreceptors (‘rod-like’, ‘blue’ cone and ‘green’ cone) present in the 13-lined ground squirrel the green cones are the overwhelming majority. The dark-adapted b-wave had two components: a b₁-wave with a spectral sensitivity that fitted a 516 ± 1 nm Dartnall nomogram and a b₂-wave with a spectral sensitivity that fitted a 502 ± 4 nm Dartnall nomogram. The light-adapted b-wave had a spectral sensitivity that fitted a 516 ± 2 nm Dartnall nomogram.     

Conditioning lesion effects on rat sciatic nerve regeneration are influenced by electrical stimulation delivered to denervated muscles

The rate of regeneration and the initial delay of the fastest growing fibers of the rat sciatic nerve were electrophysiologically evaluated after a freeze at mid-thigh. A prior section or a prior freeze at the ankle level increased the rate of regeneration and decreased the initial delay with different magnitudes. These phenomena are named ‘conditioning lesion effects’. A daily electrical stimulation transcutaneously delivered to the foot sole muscles from the day following their denervation by the prior lesion did not modify the increased rate of regeneration but prevented the decrease of the initial delay whatever the type of the prior lesion. Therefore, the initiation of earlier sprouting of the parent axons seems to be specifically controlled by a signal associated with muscle denervation properties.     

Selective impairment of declarative memory following stimulation of dentate gyrus granule cells: a naloxone-sensitive effect

Albino rats received 10 s of sub-seizure electrical stimulation applied to the dentate gyrus granule cells immediately after acquisition of information on trial 1 of a 2-trial radial maze spatial memory task. Granule cell stimulation selectively reduced the probability of accessing information held in declarative memory (‘knowing that’ a particular maze location contains food) while leaving procedural memory intact (‘knowing how’ to search for food in the maze). This specific memory impairment was prevented by pretreatment with the opiate antagonist naloxone. Naloxone also improved memory performance when given to non-stimulated subjects.