Do we have the right PROMs for measuring outcomes in lumbar spinal surgery?

PURPOSE: Patient-reported outcome measures (PROMs) have become an important part of routine auditing of outcomes in spinal surgery in the UK. PROMs can be used to help assess the quality of care provided by surgical units by determining the comparative health status of patients, before and after surgery. This study was designed to review the PROMs used to assess outcomes in spinal surgery and to determine if they are fit for the purpose. METHODS: A systematic literature search was undertaken to identify studies that reported PROMs data following lumbar spinal surgery. The PROMs that were used in each study were recorded and a separate search was undertaken to determine the evidence regarding the validity of each measure. RESULTS: The initial search identified 1142 abstracts, which were reduced through de-duplication, filtering and review to 58 articles, which were retrieved and reviewed in full. The search identified that the majority of studies used either the Oswestry Disability Index (ODI), SF-36, Roland-Morris Disability Questionnaire (RMDQ) and EQ-5D along with visual analogue scales or numeric rating scales for back and leg pain. CONCLUSIONS: The consistent use of PROMs supports the comparison of outcomes from different studies, although there was minimal evidence regarding the specificity and sensitivity of these measures for use with lumbar spinal patients. Our review highlights the need to determine a consensus regarding the use and reporting of outcome measures within the lumbar spine literature.

Entorhinal cortex volume in older adults: reliability and validity considerations for three published measurement protocols.

Measuring the entorhinal cortex (ERC) is challenging due to lateral border discrimination from the perirhinal cortex. From a sample of 39 nondemented older adults who completed volumetric image scans and verbal memory indices, we examined reliability and validity concerns for three ERC protocols with different lateral boundary guidelines (i.e., Goncharova, Dickerson, Stoub, & deToledo-Morrell, 2001; Honeycutt et al., 1998; Insausti et al., 1998). We used three novice raters to assess inter-rater reliability on a subset of scans (216 total ERCs), with the entire dataset measured by one rater with strong intra-rater reliability on each technique (234 total ERCs). We found moderate to strong inter-rater reliability for two techniques with consistent ERC lateral boundary endpoints (Goncharova, Honeycutt), with negligible to moderate reliability for the technique requiring consideration of collateral sulcal depth (Insausti). Left ERC and story memory associations were moderate and positive for two techniques designed to exclude the perirhinal cortex (Insausti, Goncharova), with the Insausti technique continuing to explain 10% of memory score variance after additionally controlling for depression symptom severity. Right ERC-story memory associations were nonexistent after excluding an outlier. Researchers are encouraged to consider challenges of rater training for ERC techniques and how lateral boundary endpoints may impact structure-function associations.

The in vitro antibiofilm activity of selected culinary herbs and medicinal plants against Listeria monocytogenes.

AIMS: The antibiofilm activity of extracts obtained from selected herbs, spices, beverages and commercially important medicinal plants was investigated on Listeria monocytogenes. METHODS AND RESULTS: The growth and development of the biofilm was assessed using the crystal violet (CV) assay. The respiratory activity was assessed using the 2, 3-bis [2-methyloxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide (XTT) reduction assay. The majority of extracts tested prevented cell adhesion to the polyvinyl chloride (PVC) surface. Seven of the 15 extracts reduced biofilm adhesion of both the clinical and the type strains by at least 50%. In contrast, inhibition of a preformed biofilm was more difficult to achieve, with only three extracts (Rosmarinus officinalis, Mentha piperita and Melaleuca alternifolia) inhibiting the growth of both strains by at least 50%. CONCLUSIONS: Although most extracts were able to reduce initial cell attachment, inhibition of growth in a preformed biofilm was more difficult to achieve. SIGNIFICANCE AND IMPACT OF THE STUDY: The ability to reduce biofilm biomass as shown by several plant extracts warrants further investigation to explore the use of natural products in antibiofilm adhesion.

Kernel Fisher discriminant for shape-based classification in epilepsy.

In this paper, we present the application of kernel Fisher discriminant in the statistical analysis of shape deformations that indicate the hemispheric location of an epileptic focus. The scans of two classes of patients with epilepsy, those with a right and those with a left anterior medial temporal lobe focus (RATL and LATL), as validated by clinical consensus and subsequent surgery, were compared to a set of age and sex matched healthy volunteers using both volume and shape based features. Shape-based features are derived from the displacement field characterizing the non-rigid deformation between the left and right hippocampi of a control or a patient as the case may be. Using the shape-based features, the results show a significant improvement in distinguishing between the controls and the rest (RATL and LATL) vis-a-vis volume-based features. Using a novel feature, namely, the normalized histogram of the 3D displacement field, we also achieved significant improvement over the volume-based feature in classifying the patients as belonging to either of the two classes LATL or RATL, respectively. It should be noted that automated identification of hemispherical foci of epilepsy has not been previously reported.

Exploiting human anatomical variability as a link between genome and cognome.

Although talents and disabilities appear to run in families, direct links between genes and cognitive ability are difficult to establish. Investigators are currently searching for intermediate phenotypes with plausible links to both genome and cognome (the cognitive phenotype). Cortical anatomy could provide one such intermediate phenotype. Variation in cortical size, asymmetry and sulcal pattern is influenced by genetic variation in neurotrophic factors and can predict variation in verbal and mathematical talent. Anecdotal evidence suggests that individuals with a rare morphological variant of Sylvian fissure sometimes have superior visualization ability combined with verbal deficits. Documentation of such 'cognitive cortical syndromes' might prove as genetically informative as the identification of dysmorphic syndromes associated with mental retardation. A necessary prerequisite for the establishment of such syndromes is a reliable technique for the identification of cortical patterns. Recent technical advances in software for automatically labeling and measuring cortical sulci now provide the possibility of establishing standard measures for their shape, size and location. Such measures are a prerequisite for genetic studies of cortical patterns that could illuminate the neurodevelopmental pathways by which genes affect cognitive ability.

Image registration via level-set motion: applications to atlas-based segmentation.

Image registration is an often encountered problem in various fields including medical imaging, computer vision and image processing. Numerous algorithms for registering image data have been reported in these areas. In this paper, we present a novel curve evolution approach expressed in a level-set framework to achieve image intensity morphing and a simple non-linear PDE for the corresponding coordinate registration. The key features of the intensity morphing model are that (a) it is very fast and (b) existence and uniqueness of the solution for the evolution model are established in a Sobolev space as opposed to using viscosity methods. The salient features of the coordinate registration model are its simplicity and computational efficiency. The intensity morph is easily achieved via evolving level-sets of one image into the level-sets of the other. To explicitly estimate the coordinate transformation between the images, we derive a non-linear PDE-based motion model which can be solved very efficiently. We demonstrate the performance of our algorithm on a variety of images including synthetic and real data. As an application of the PDE-based motion model, atlas based segmentation of hippocampal shape from several MR brain scans is depicted. In each of these experiments, automated hippocampal shape recovery results are validated via manual "expert" segmentations.

Planar asymmetry tips the phonological playground and environment raises the bar.

Reading readiness varies as a function of family and environmental variables. This study of 11-year-old children (N = 39) was designed to determine if there was an additional or interactive contribution of brain structure. Evidence is presented that both environmental and biological variables predict phonological development. Temporal lobe (planar) asymmetry, hand preference, family history of reading disability, and SES explained over half of the variance in phonological and verbal performance. The results demonstrate a linear association between cerebral organization and phonological skill within socioeconomic groups. These data provide concrete evidence to support the commonly held assumption that both environmental and biological factors are independent determinants of a child's ability to process linguistic information.

Relative shift in activity from medial to lateral frontal cortex during internally versus externally guided word generation.

Goldberg (1985) hypothesized that as language output changes from internally to externally guided production, activity shifts from supplementary motor area (SMA) to lateral premotor areas, including Broca's area. To test this hypothesis, 15 right-handed native English speakers performed three word generation tasks varying in the amount of internal guidance and a repetition task during functional magnetic resonance imaging (fMRI). Volumes of significant activity for each task versus a resting state were derived using voxel-by-voxel repeated-measures t tests (p <.001) across subjects. Changes in the size of activity volumes for left medial frontal regions (SMA and pre-SMA/BA 32) versus left lateral frontal regions (Broca's area, inferior frontal sulcus) were assessed as internal guidance of word generation decreased and external guidance increased. Comparing SMA to Broca's area, Goldberg's hypothesis was not verified. However, pre-SMA/BA 32 activity volumes decreased significantly and inferior frontal sulcus activity volumes increased significantly as word generation tasks moved from internally to externally guided.

Anatomical risk factors for phonological dyslexia.

Successful behavioral genetic studies require precise definition of a homogenous phenotype. This study searched for anatomical markers that might restrict variability in the reading disability phenotype. The subjects were 15 college students (8 male/7 female) diagnosed with a reading disability (RD) and 15 controls (8 males/7 females). All subjects completed a cognitive and reading battery. Only 11 of the RD subjects had a phonological deficit [phonological dyslexia (PD): pseudo word decoding scores < 90 (27th percentile)]. Thirteen RD (9 PD) and 15 controls received a volumetric MRI scan. Four anatomical measures differentiated the PD group from the remainder of the subjects: (i) marked rightward cerebral asymmetry, (ii) marked leftward asymmetry of the anterior lobe of the cerebellum, (ii) combined leftward asymmetry of the planum and posterior ascending ramus of the sylvian fissure, and (iv) a large duplication of Heschl's gyrus on the left. When these four measures were normalized and summed, the resulting variable predicted short- and long-term phonological memory. By contrast, oral and written comprehension skills were predicted by a different anatomical variable: low cerebral volume. These findings provide neurobiological support for an RD phenotype characterized by phonological deficits in the presence of normal or superior comprehension. The study of individual variation in cortical structure may provide a useful link between genotype and behavior.

Working memory deficits in schizophrenia are not necessarily specific or associated with MRI-based estimates of area 46 volumes.

Despite substantial evidence that the prefrontal cortex does not function normally in patients diagnosed with schizophrenia, evidence for prefrontal structural abnormalities, as measured by magnetic resonance imaging (MRI), has been inconsistent. Additionally, evidence for relationships between prefrontal structural and functional measures has been limited. The inconsistencies in the MRI literature are, at least in part, due to a lack of standard and specific measurement protocols that allow delineation of functionally distinct cortical regions. In this study, reliable methods for measuring an estimate of area 46 (estimate referred to as area 46(e)), as defined by 'Cereb. Cortex 5 (1995) 323', were developed and used to examine relationships between area 46(e) volumes, working memory, and symptom severity in 23 male patients and 23 healthy male comparison subjects. Patients performed more poorly than healthy reference subjects on all cognitive measures including measures of spatial and non-spatial working memory, but showed no significant corresponding deficits in area 46(e) volumes or whole brain volumes. Moreover, there were no significant relationships between symptom severity and area 46(e) volumes. These findings suggest that the prefrontal functional abnormalities observed in schizophrenia may occur in the absence of prefrontal volume deficits, and may instead involve more widespread brain systems or prefrontal connections with other brain regions.

Structural imaging in dyslexia: the planum temporale.

The search for a neurobiological substrate for dyslexia has focused on anomalous planum symmetry. The results of imaging studies of the planum have been inconsistent, perhaps due to diagnostic uncertainty, technical differences in measurement criteria, and inadequate control of handedness, sex, and cognitive ability. Although structural imaging studies have not clarified the neurobiology of reading disability, converging evidence suggests that variation in asymmetry of the planum temporale does have functional significance. Studies in a variety of populations have shown a significant association between planar asymmetry, the strength of hand preference, and general verbal skills such as vocabulary and comprehension. Future structural imaging studies of dyslexia should match participants on hand preference and general verbal ability in order to determine the relationship between brain structure and written and oral language.

Digitizing the moving face during dynamic displays of emotion.

Humans typically decode facial signals during dynamic interactions in which the face moves. In this study, we digitized real time video signals in order to examine movement asymmetries across the face during emotional and nonemotional expressions. Forty dextral males were tested. For each expression, a 400 ms video segment was analyzed for changes in signal value (pixel intensity) over consecutive frames. The upper and lower face regions were examined separately due to differences in the cortical enervation of facial muscles in the upper (bilateral) vs lower face (contralateral). Results revealed distinctly different movement asymmetries over the lower and upper hemiface. In the upper face, more movement occurred over the right side for most facial expressions, regardless of emotionality. The latter finding questions the assumption that muscles of the upper face are symmetrical and/or bilaterally enervated in a symmetrical manner. In the lower face, negative expressions linked to fight-flight emotions (i.e. fear, anger) were associated with greater left sided movement, whereas happiness tended to be associated with more right sided movement. No consistent pattern of movement asymmetry occurred for nonemotional expressions. Although the valence-related movement asymmetries in the lower face are consistent with neuropsychological models of emotional expressivity, it remains unclear whether they reflect activation or inhibitory hemispheric mechanisms. Taken together, these data suggest that multiple factors may contribute to expressive movement asymmetries of the face.

LOFA: software for individualized localization of functional MRI activity.

Although PET, SPECT, and fMRI studies have led to significant advances in functional mapping of the human brain, precise localization and quantification of activity in individual brains require additional procedures. Difficulties to be addressed by a localization strategy are: resolution of individual anatomic differences, differentiation of functional activity in closely juxtaposed brain regions, and management of multiple intricately shaped 3D anatomic structures. In this paper, we describe a localization tool, LOFA, which addresses these problems by forming ROIs with a user-driven interface. Using LOFA, complex 3D anatomy can be defined through open or closed loops and anatomic landmarks. Resulting partitions can be overlaid on top of each other to form multiple regions of interest (ROIs), and functional activity in these ROIs can be extracted individually, one after the other. LOFA introduces important paradigmatic advances over the other ROI analysis methods. The toolbox is interactive, fully compatible with AFNI (MCW), and requires Pv-Wave (VNI Inc.) license to run.

Cumulative effect of anatomical risk factors for schizophrenia: an MRI study.

BACKGROUND: Although schizophrenic and control subjects differ on a variety of neuroanatomical measures, the specificity and sensitivity of any one measure for differentiating between groups are low. This study investigated the cumulative effect of deviant brain structure on diagnosis. METHODS: Hemisphere and third ventricle volume and the normalized (Talairach) location of three association cortex sulcal landmarks were measured on high-resolution MRI scans in 37 male patients with schizophrenia and 33 male control subjects matched on age, handedness, and parental socioeconomic status. RESULTS: While there were few group differences on individual anatomical measures, the 10 variables reliably discriminated between the two groups when used in concert in a discriminant function analysis (F[10.59] = 3.6, p < .0009) with 77% of the subjects correctly classified. Five of the measures (left posterior cingulate, left inferior frontal sulcus, right sylvian fissure, and left and right halves of the third ventricle) correlated significantly with the discriminant function (p < .005). CONCLUSIONS: This is the first study to demonstrate that schizophrenics can be distinguished from matched controls on the basis of brain anatomy alone. The risk of schizophrenia may depend on the total amount of neural deviance, rather than on anomalies in a single structure or circuit.

Activity in the paracingulate and cingulate sulci during word generation: an fMRI study of functional anatomy.

The supracallosal medial frontal cortex can be divided into three functional domains: a ventral region with connections to the limbic system, an anterior dorsal region with connections to lateral prefrontal systems, and a posterior dorsal region with connections to lateral motor systems. Lesion and functional imaging studies implicate this medial frontal cortex in speech and language generation. The current functional magnetic resonance imaging (fMRI) study of word generation was designed to determine which of these three functional domains was substantially involved by mapping individual subjects' functional activity onto structural images of their left medial frontal cortex. Of 28 neurologically normal right-handed participants, 21 demonstrated a prominent paracingu- late sulcus (PCS), which lies in the anterior dorsal region with connections to lateral prefrontal systems. Activity increases for word generation centered in the PCS in 18 of these 21 cases. The posterior dorsal region also demonstrated significant activity in a majority of participants (16/28 cases). Activity rarely extended into the cingulate sulcus (CS) (3/21 cases) when there was a prominent PCS. If there was no prominent PCS, however, activity did extend into the CS (6/7 cases). In no case was activity present on the crest of the cingulate gyrus, which is heavily connected to the limbic system. Thus, current findings suggest that medial frontal activity during word generation reflects cognitive and motor rather than limbic system participation. The current study demonstrates that suitably designed fMRI studies can be used to determine the functional significance of anatomic variants in human cortex.

Influence of speech stimuli intensity on the activation of auditory cortex investigated with functional magnetic resonance imaging.

Understanding the impact of variations in the acoustic signal is critical for the development of auditory and language fMRI as an experimental tool. We describe the dependence of the BOLD signal and speech intelligibility on the intensity of auditory stimuli. Eighteen subjects were imaged on a 1.5-T MRI scanner. Speech stimuli were English monosyllabic words played at five intensity levels. Intrasubject reproducibility was measured on one subject by presenting the stimulus five times at the same intensity level. Intelligibility was measured during data acquisition as subjects signaled when hearing two targets. Each functional trial consisted of four cycles (30 s off-30 s on). Five oblique slices covering primary and association auditory areas were imaged. Activated voxels were identified by cross-correlation analysis and their percent signal change (delta S) was measured. Intersubject differences in activation extent, asymmetry, and dependence on intensity were striking. Volume of activation was significantly greater in the left than in the right hemisphere. Intrasubject reproducibility for delta S was higher than for volume of activation. delta S and intelligibility showed a similar dependence on intensity suggesting that not only intensity but also intelligibility affect the fMRI signal.

Normal variation in the frequency and location of human auditory cortex landmarks. Heschl's gyrus: where is it?

Interpersonal communication via the auditory modality is fundamental to normal human development. One of the prominent anatomical specializations supporting this communication is the transverse gyrus of Heschl on the superior surface of the temporal lobe. This gyrus frequently appears duplicated, either by a sulcus indenting the crown of an initially single gyrus (common stem), or by a complete posterior duplication. The frequency of these duplications has been reported to be elevated in populations with learning disabilities and genetic anomalies. The significance of this observation is unclear, however, due to conflicting reports of the base rate of duplication and the location of relevant sulcal landmarks. In this study we report the variation in frequency and location of the sulcal boundaries of Heschl's gyrus in volumetric magnetic resonance imaging scans of 105 normal controls aged 5-65. The major results were as follows: (i) duplications were unstable--the frequency of duplication ranged from 20 to 60% depending on distance from the midline; (ii) common stem duplications were more frequent than posterior duplications, particularly in the right hemisphere. Intra- and interindividual instability in sulcal landmarks pose serious obstacles to the attempt to map behavioral function onto the brain. Novel methods for dealing with structural variation are needed to facilitate the development of valid mapping techniques.

Hand preference and magnetic resonance imaging asymmetries of the central sulcus.

Hand preference is perhaps the most evident behavioral asymmetry observed in humans. Anatomic brain asymmetries that may be associated with hand preference have not been extensively studied, and no clear relationship between asymmetries of the motor system and hand preference have been established. Therefore, using volumetric magnetic resonance imaging methodologies, the surface area of the hand representation was measured along the length of the central sulcus in 15 consistent right- and 15 left-handers matched for age and gender. There was a significant leftward asymmetry of the motor hand area of the precentral gyrus in the right-handers, but no directional asymmetry was found in the left-handers. When asymmetry quotients were computed to determine the distribution of interhemispheric asymmetries, the left motor bank was greater than the right motor bank in 9 of 15 right-handers, the right motor bank was greater than the left motor bank in 3 of 15 right-handers, and the motor banks were equal in 3 of 15 right-handers. In contrast, among left-handers, the left motor bank was greater than the right motor bank in 5 of 15, the right motor bank was greater than the left motor bank in 5 of 15, and the motor banks were equal in 5 of 15. Although no direct measure of motor dexterity and skill was performed, these data suggest that anatomic asymmetries of the motor hand area may be related to hand preference because of the differences in right-handers and left-handers. Furthermore, the predominant leftward asymmetry in right-handers and the random distribution of asymmetries in the left-handers support Annett's right-shift theory. It is unclear, however, whether these asymmetries are the result of preferential hand use or are a reflection of a biologic preference to use one limb over the other.

An efficient motion estimator with application to medical image registration.

Image registration is a very important problem in computer vision and medical image processing. Numerous algorithms for registering single and multi-modal image data have been reported in these areas. Robustness as well as computational efficiency are prime factors of importance in image data registration. In this paper, a robust/reliable and efficient algorithm for estimating the transformation between two image data sets of a patient taken from the same modality over time is presented. Estimating the registration between two image data sets is formulated as a motion-estimation problem. We use a hierarchical optical flow motion model which allows for both global as well as local motion between the data sets. In this hierarchical motion model, we represent the flow field with a B-spline basis which implicitly incorporates smoothness constraints on the field. In computing the motion, we minimize the expectation of the squared differences energy function numerically via a modified Newton iteration scheme. The main idea in the modified Newton method is that we precompute the Hessian of the energy function at the optimum without explicitly knowing the optimum. This idea is used for both global and local motion estimation in the hierarchical motion model. We present examples of motion estimation on synthetic and real data (from a patient acquired during pre- and post-operative stages) and compare the performance of our algorithm with that of competing ones.

Deficits in auditory temporal and spectral resolution in language-impaired children.

Between 3 and 6 per cent of children who are otherwise unimpaired have extreme difficulties producing and understanding spoken language. This disorder is typically labelled specific language impairment. Children diagnosed with specific language impairment often have accompanying reading difficulties (dyslexia), but not all children with reading difficulties have specific language impairment. Some researchers claim that language impairment arises from failures specific to language or cognitive processing. Others hold that language impairment results from a more elemental problem that makes affected children unable to hear the acoustic distinctions among successive brief sounds in speech. Here we report the results of psychophysical tests employing simple tones and noises showing that children with specific language impairment have severe auditory perceptual deficits for brief but not long tones in particular sound contexts. Our data support the view that language difficulties result from problems in auditory perception, and provide further information about the nature of these perceptual problems that should contribute to improving the diagnosis and treatment of language impairment and related disorders.