The Light-Dosimeter: A new device to help advance research on the non-visual responses to light.

This article describes the development of a device to investigate the non-visual responses to light: The Light-Dosimeter (lido). Its multidisciplinary team followed a user-centred approach throughout the project, that is, their design decisions focused on researchers' and participants' needs. Together with custom-made mountings and the software Lido Studio, the lidos provide researchers with a holistic solution to record participants' light exposure in the near-corneal plane in laboratory settings and under real-world conditions. Validation measurements with commercial equipment were deemed satisfying, as was the combining with data from other devices. The handling of the lidos and mountings and the use of the software Lido Studio during the trial period by various researchers and participants were successful. Despite some limitations, the lidos can help advance research on the non-visual responses to light over the coming years.

Cognition and cerebrovascular function in primary hyperparathyroidism before and after parathyroidectomy.

PURPOSE: There are cognitive changes in primary hyperparathyroidism (PHPT) that improve with parathyroidectomy, but the mechanism of cognitive dysfunction has not been delineated. We assessed if cerebrovascular function is impaired in PHPT, improves post-parathyroidectomy and is associated with PTH level and cognitive dysfunction. METHODS: This is an observational study of 43 patients with mild hypercalcemic or normocalcemic PHPT or goiter. At baseline, cerebrovascular function (dynamic cerebral autoregulation and vasomotor reactivity) by transcranial Doppler and neuropsychological function were compared between all three groups. A subset underwent parathyroidectomy or thyroidectomy, and was compared 6 months post-operatively. RESULTS: Mean cerebrovascular and neuropsychological function was normal and no worse in PHPT compared to controls preoperatively. Higher PTH was associated with worse intracerebral autoregulation (r = - 0.43, p = 0.02) and worse cognitive performance on some tests. Post-parathyroidectomy, mood improved significantly, but changes did not differ compared to those having thyroidectomy (p = 0.84). There was no consistent improvement in cognition or change in vascular function in either surgical group. CONCLUSIONS: Although higher PTH was associated with worse intracerebral autoregulation, cerebrovascular function, cognition and mood were normal in mild PHPT. PTX did not improve vascular or cognitive function. The observed improvement in mood cannot be clearly attributed to PTX. Notwithstanding the small sample size, the results do not support changing current criteria for parathyroidectomy to include cognitive complaints. However, the associations between PTH, cognition and cerebral autoregulation merit future studies in those with more severe hyperparathyroidism.

Unstable Plaque is a Treatable Cause of Cognitive Decline.

While many risk factors are modifiable, there remains a compelling need for novel approaches to prevent cognitive impairment. We propose that unstable carotid plaque causes microemboli that, in turn, cause microinfarcts and other adverse pathophysiological cerebral processes, which individually do not manifest clinically but cumulatively manifest as cognitive decline and ultimately cognitive impairment. Animal models support multiple cerebral microemboli having adverse effects on cognition. By addressing the source for microembolization by endarterectomy or stenting, patients with high-grade atherosclerotic stenosis may have better cognitive outcomes. If our hypothesis is verified, then treatment of carotid plaque at elevated risk of generating cerebral microemboli would be effective in preserving cognition, regardless of whether the stenosis is high-grade or causing cerebral hemispheric hypoperfusion.

Variability in language recovery after first-time stroke.

BACKGROUND: Predicting aphasia recovery after stroke has been difficult due to substantial variability in outcomes. Few studies have characterised the nature and extent of recovery, beginning with baselines at 24-72 hours after stroke onset. AIM: To characterise the course of language recovery after first-time stroke. METHODS: Using our Performance and Recovery in Stroke Study (PARIS) database, we evaluated consecutive first-time stroke patients with aphasia and diffusion-weighted-image-positive lesions on admission and at 90 days. RESULTS: Twenty-two of 91 patients had language disorders. Initial syndrome scores were positively correlated with 90-day scores (r = 0.60) and negatively correlated with the change in score from baseline to follow-up (r = -0.66). Neither lesion size, age nor education correlated with initial syndrome severity or with performance at 90 days. Level of education was not associated with degree of recovery. A multiple regression model that combined lesion size, age and initial syndrome was significant (p = 0.03) but only explained 29% of the variance. Patients with severe deficits at baseline in individual language domains could recover, improve to a less severe deficit or not improve at all. CONCLUSION: There was significant variability in language recovery after first-time stroke, even in more severe, initial syndromes. Traditional predictors of post-stroke language outcomes did not reliably predict function at 90 days. These data suggest that other factors that account for functional stroke recovery have not yet been identified.

Ipsilateral motor dysfunction from unilateral stroke: implications for the functional neuroanatomy of hemiparesis.

BACKGROUND: Motor dysfunction in the contralateral hand has been well characterised after stroke. The ipsilateral hand has received less attention, yet may provide valuable insights into the structure of the motor system and the nature of the recovery process. By tracking motor function of both hands beginning in the acute stroke period in patients with cortical versus subcortical lesions, we sought to understand the functional anatomy of the ipsilateral deficit. METHODS: We examined 30 patients with first-ever unilateral hemiparetic stroke, 23 with subcortical lesions affecting the corticospinal tract, seven with cortical involvement. Patients performed hand dynamometry and the 9-Hole Peg Test (9HPT) with each hand at 24-48 h, 1 week, 3 months and 1 year after stroke. Linear regression was used to compare the two different motor tasks in each hand. Repeated measures ANOVA was used to compare recovery rates of the two tasks in the first 3 months. RESULTS: Ipsilateral 9HPT scores averaged z = -7.1, -3.6, -2.5 and -2.3 at the four time points whereas grip strength was unaffected. The initial degree of impairment of grip strength in the contralateral hand did not correlate with the degree of impairment of 9HPT in either the contralateral or ipsilateral hand (r = 0.001, p = 0.98), whereas the initial degree of impairment of 9HPT in the contralateral hand correlated with the degree of impairment of 9HPT in the ipsilateral hand (r = 0.79, p = 0.035). The rate of recovery also differed for the two tasks (p = 0.005). CONCLUSION: Ipsilateral motor deficits are demonstrable immediately after stroke and extend into the subacute and chronic recovery period. Dissociation between grip strength and dexterity support the notion that dexterity and grip strength operate as anatomically and functionally distinct entities. Our findings in patients with subcortical lesions suggest that the model of white matter tract injury needs to be refined to reflect the influence of a subcortical lesion on bi-hemispheral cortical networks, rather than as a simple "severed cable" model of disruption of corticofugal fibres. Our data have implications for both stroke clinical trials and the development of new strategies for therapeutic intervention in stroke recovery.

The development of a weak anion micro-capillary film for protein chromatography.

In this study, the surface of a microporous walled micro-capillary film (MMCF) was modified into a weak anion exchanger by coupling cyanuric chloride and 2-diethylaminoethylamine (DEAE) to the ethylene-vinyl alcohol (EVOH) matrix. Fourier transform infrared spectroscopy (FTIR) measurements of modified and unmodified MMCFs confirmed the addition of a triazine ring and DEAE onto the membrane. Binding of bovine serum albumin (BSA) at pH 7.2 was found to follow a Langmuir isotherm with a maximum equilibrium binding of 12.4mg BSA/mL adsorbent and 8.2mg BSA/mL adsorbent under static and flow conditions, respectively. The ion exchange capacity, determined by Mohr's titration of chlorine atoms displaced from the functionalised surface, was found to be 195±21µmol Cl-/mL of adsorber, comparable to commercial ion exchangers. BSA adsorption onto the ion exchanger was strongly pH-dependant, with an observed reduction in binding above pH 8.2. Frontal experiments of a BSA (5mg/mL) and lysozyme (5mg/mL) mixture demonstrated successful separation of BSA from lysozyme at more than 97% purity as verified by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). Separation between similarly charged anionic molecules was also achieved using BSA (5mg/mL) and herring sperm DNA (0.25mg/mL). BSA was extracted at 100% purity, demonstrating the ability of MMCF-DEAE to remove significant DNA contamination from a protein solution. These experiments highlight the potential for MMCFs to be used for fast protein purification in preparative chromatography application.

Spectral integration in primary auditory cortex: laminar processing of afferent input, in vivo and in vitro.

Auditory cortex neurons integrate information over a broad range of sound frequencies, yet it is not known how such integration is accomplished at the cellular or systems levels. Whereas information about frequencies near a neuron's characteristic frequency is likely to be relayed to the neuron by lemniscal thalamocortical inputs from the ventral division of the medial geniculate nucleus, we recently proposed that information about frequencies spectrally distant from characteristic frequency is mainly relayed to the neuron via "horizontal" intracortical projections from neurons with spectrally-distant characteristic frequencies [J Neurophysiol 91 (2004) 2551]. Here we test this hypothesis by using current source density analysis to determine if characteristic frequency and spectrally-distant non-characteristic frequency stimuli preferentially activate thalamocortical and horizontal pathways, respectively, in rat auditory cortex. Characteristic frequency stimuli produced current source density profiles with prominent initial current sinks in layers 3 and 4--the termination zone of lemniscal inputs from medial geniculate nucleus. In contrast, stimuli three octaves below characteristic frequency produced initial current sinks mainly in the infragranular layers. Differences between current source density profiles were only apparent for initial current sinks; profiles for longer-latency current sinks evoked by characteristic frequency and non-characteristic frequency stimuli overlapped to a greater degree, likely due to shared mechanisms of intracortical processing or to longer-latency thalamocortical contributions (lemniscal and nonlemniscal). To identify current source density profiles produced by activation of lemniscal thalamocortical inputs alone, we utilized the mouse auditory thalamocortical slice preparation. Electrical stimulation of the medial geniculate nucleus in vitro produced major current sinks in cortical layers 3/4, and excitation spread horizontally from this point throughout primary auditory cortex to produce current sinks in multiple cortical layers. These data support the hypothesis that relay of thalamocortical information throughout auditory cortex via horizontal intracortical projections may be the basis of broad spectral integration in vivo.

Effect of bore fluid composition on microstructure and performance of a microporous hollow fibre membrane as a cation-exchange substrate.

Micro-capillary film (MCF) membranes are effective platforms for bioseparations and viable alternatives to established packed bed and membrane substrates at the analytical and preparative chromatography scales. Single hollow fibre (HF) MCF membranes with varied microstructures were produced in order to evaluate the effect of the bore fluid composition used during hollow fibre extrusion on their structure and performance as cation-exchange adsorbers. Hollow fibres were fabricated from ethylene-vinyl alcohol (EVOH) copolymer through solution extrusion followed by nonsolvent induced phase separation (NIPS) using bore fluids of differing composition (100wt.% N-methyl-2-pyrrolidone (NMP), 100wt.% glycerol, 100wt.% water). All HFs displayed highly microporous and mesoporous microstructures, with distinct regions of pore size <1µm, 5-15µm and up to 50µm in diameter, depending upon proximity to the bore fluid. Scanning electron microscopy (SEM) revealed skins of pore size <1µm at the inner surface of HFs produced with water and glycerol, while NMP bore fluid resulted in a skinless inner HF surface. The HFs were modified for chromatography by functionalising the polymer surface hydroxyl groups with sulphonic acid (SP) groups to produce cation-exchange adsorbers. The maximum binding capacities of the HFs were determined by frontal analysis using lysozyme solutions (0.05-100mgml(-1)) for a flow rate of 1.0mlmin(-1). The NMP-HF-SP module displayed the largest maximum lysozyme binding capacity of all the fibres produced (40.3mg lysozyme/ml adsorbent volume), a nearly 2-fold increase over the glycerol and 10-fold increase over the water variants at the same sample flow rate. The importance of NMP as a bore fluid to hollow fibre membrane performance as a result of inner surface porosity was established with a view to applying this parameter for the optimisation of multi-capillary MCF performance in future studies.

Anxiety disorders in a neuromuscular clinic.

Twenty patients with myasthenia gravis and 15 patients with polymyositis/dermatomyositis were assessed with a structured interview. Fifteen patients (43%) were diagnosed with an anxiety disorder. Significantly more myasthenic patients (40%) than polymyositis/dermatomyositis patients (7%) were diagnosed with panic disorder/agoraphobia. These findings suggest that the symptoms of myasthenia gravis may predispose vulnerable individuals to panic disorder/agoraphobia.

Distinct syndromes of hemineglect.

Hemineglect was assessed in 34 patients with right-hemisphere stroke using a letter-cancellation task and a line bisection task. No significant correlation (r = .39) was found between scores on the two tests. Ten patients who showed neglect on the cancellation task but performed normally on line bisection had frontal or deep lesions. Eleven patients with posterior lesions deviated rightward on line bisection; several of these had minimal or no cancellation deficit. A nonmotor task involving judgment of a bisected line was also performed abnormally by six patients with line bisection shift, suggesting that such shift does not result from a motor response asymmetry. We propose that separable components of the neglect syndrome may be associated with damage to discrete areas of the nondominant hemisphere.

Developmental deficits in adult patients with arteriovenous malformations.

BACKGROUND: Cerebral arteriovenous malformations (AVMs) are congenital masses of arteries and veins that appear to undergo an unclear "maturation" for many years. Using structured interviews, we compared developmental history of adult patients with AVM with a comparison group of patients with cerebral tumor or aneurysm. OBJECTIVE: To determine whether a remote history of developmental abnormality in adult patients with AVM might be an early marker of cerebral status. DESIGN: Adult patients with AVM and a comparison group of patients with cerebral aneurysm or low-grade tumor participated in a survey. SETTING: Urban medical school-based tertiary care center. PATIENTS: Forty-four randomly selected patients with AVM from the Columbia-Presbyterian AVM Database. There were 32 comparison patients:15 randomly chosen patients from the institution's Cerebral Aneurysm Database and all 17 patients who underwent a biopsy from 1990 to 1995 with a diagnosis of low-grade tumor and who could be contacted. MAIN OUTCOME MEASURES: A brief, structured interview adapted from the Centers for Disease Control and Prevention for its 1994 study of the prevalence of learning disabilities in American children. We defined the positive occurrence of a condition as an affirmative answer to the question, " Did have (condition) during his/her school-age years?" Each patient was also asked if there had been any problems in the following skill areas: reading, writing, listening, speaking, attention, impulsivity, organization, mathematics, or drawing. The AVM size was calculated on the angiographic film by measuring its longest diameter in any dimension. RESULTS: Patients with AVM were significantly more likely to report a positive occurrence to any survey question (P<.05). Two thirds of all patients with AVM (66%) reported at least 1 skill difficulty during their school years, significantly more than the comparison group (P<.001). Neither the maximum AVM diameter nor the occurrence of hemorrhage as an adult differed between patients with AVM with and without early skill difficulty. CONCLUSIONS: Patients with AVM are more likely to report a developmental learning disorder than patients with tumor or aneurysm despite the absence of other neurologic symptoms of diseases not diagnosed for another 20 years. These data support the notion that disorders of behavioral and intellectual function are sensitive markers of early cerebral status.

Multifocal central nervous system damage caused by toluene abuse.

Four toluene abusers had evidence of severe multifocal central nervous system damage. Impairment of cognitive, cerebellar, brainstem, auditory, and pyramidal tract function, as well as CT evidence of cerebral cortical, cerebellar, and brainstem atrophy, have been noted. In addition, we found opsoclonus, ocular flutter, and ocular dysmetria. All three patients tested had abnormal brainstem auditory evoked potentials, indicative of brainstem dysfunction. The patient with opsoclonus had CT evidence of brainstem, cerebellar, and cerebral cortical atrophy.

Pure topographic disorientation: A distinctive syndrome with varied localization.

Pure topographic disorientation (TD), defined as impaired recall of routes in familiar surroundings, has been attributed to lesions of the right parahippocampus. The authors present three patients encountered consecutively with TD and compare them to previously published cases. Lesions causing TD included a right splenial/cuneus infarct, a right > left medial temporo-occipital infarct, and a left splenial infarct. TD as an isolated symptom may occur from lesion in a variety of posterior medial locations, including the parahippocampus, splenium, and retrosplenial cortex.

The experience of Wernicke's aphasia.

The authors induced a transient Wernicke's aphasia in a patient with left frontal arteriovenous malformation by superselective Wada injection exclusively into the lower division of the left middle cerebral artery. The patient was then asked to recall his experience, which the authors matched against his language during anesthesia. The patient's account showed that there was a more systematic attempt to respond appropriately than the authors could infer from his overt behavior. His narrative suggests that a thought process not measured by aphasia examinations may exist independent of language.

Anterior translocation of language in patients with left cerebral arteriovenous malformation.

We studied seven patients with left cerebral atriovenous malformation (AVM) with superselective arterial injection of anesthetics during angiography to determine whether there was translocation of some language functions to other regions in the ispilateral hemisphere. All patients were right handed. With a catheter inserted into each target vessel, patients underwent aphasia examination in an A-B-A design: (A) baseline, no anesthetic; (B) 1 minute after anesthetic injection; and (A) 12 minutes after injection (when its effects had dissipated). The results showed that six of seven patients had no significant aphasia at baseline or 12 minutes after anesthetic injection. One patient had a mild conduction aphasia at baseline and after anesthetic effects had dissipated. In the six patients with temporoparietal AVM, anesthetic injections into vessels in the lower division of the middle cerebral artery (MCA) not feeding the AVM (e.g., the left angular artery) produced a wide range of language function--from conduction aphasia to dense Wernicke's syndromes. When upper division MCA vessels were injected (e.g., the prefrontal branch), all developed a major aphasic disorder with significant comprehension defects. A seventh patient with a frontal opercular AVM had a mild anomia, semantic paraphasias, and decreased word-list generation when the prefrontal branch was injected. Her comprehension, however, was intact. These data show that patients with posterior cerebral AVM can show language abnormalities where such deficits are not typically seen after acute brain injury. These findings support a posterior-to-anterior extension of some language skills under conditions of brain disease.

Central poststroke pain and Wallenberg's lateral medullary infarction: frequency, character, and determinants in 63 patients.

UNLABELLED: Central poststroke pain (CPSP) is an infrequently recognized complication of lateral medullary infarction (LMI). We determined the frequency, nature, and predictors of this complication in 63 patients with LMI. The hypothesis tested was that the degree of clinical sensory loss and extent of infarction seen on MRI, both graded by a predetermined scoring scale, would be predictive of CPSP. We also performed quantitative sensory testing (QST) of thermal and pressure sensation thresholds in a subgroup of 19 patients (nine with CPSP and 10 without) to analyze in detail the spinothalamic and trigeminothalamic systems mediating these modalities from both sides of the face and body. We analyzed these results for specific markers of CPSP. RESULTS: CPSP developed in 25% (16/63) of the patients, all within 6 months. This was constant and severe with frequent allodynia, but responded in all cases to amitriptyline and recurred promptly on attempted weaning. CPSP affected the ipsilateral peri-orbital region most commonly, either alone or in combination with the contralateral limbs. Ipsilateral neurotrophic facial ulceration developed in two cases. CPSP correlated significantly (Fisher's exact test, p < 0.0002) with the degree of clinical sensory loss but not with the size of infarction seen on MRI (Fisher's exact test, p = 0.7). QST revealed a highly specific (100%) and sensitive (89%) finding for CPSP-thresholds from the check contralateral to the LMI were normal in eight of nine cases with CPSP and abnormal in all of the 10 cases without CPSP. Abnormalities in the face contralateral to the infarct are referable to the crossed trigeminothalamic tract in the medullary reticular formation medial to the infarcted lateral medulla. We conclude that this argues for the theory that central pain is caused by denervation sensitivity of the "paleo"-reticulothalamic connections due to a selective "neo"-spinothalamic lesion.

Left hemiparalexia.

Three patients with left splenial lesions made paralexic errors restricted to the left end of words. Errors appeared more frequently when a correct response was highly dependent on the initial letter of the stimulus. One patient had full visual fields with hemialexia affecting the left visual field. The other two patients had complete right hemianopia. We attribute left-sided reading errors in the hemianopic patients to a retinotopically restricted disconnection pattern that selectively disrupts transfer of information originating from the peripheral left visual field. Functional resistance of the more numerous transcallosal projections representing visual field adjacent to the vertical meridian may account for such a pattern. The emergence of positional reading errors from retinotopically restricted left hemifield disconnection suggests that callosal information transfer during normal reading may primarily involve elemental sensory rather than lexical/semantic information.

Effects of frontal lobe lesions on hypothesis sampling during concept formation.

Thirty-two subjects with unilateral cerebral tumors were assessed for the use of hypotheses and cognitive strategies during a visual discrimination task. Subjects with frontal lobe lesions attained fewer concepts and used fewer appropriate hypotheses than subjects with tumors confined to the posterior hemisphere, although there was no difference in total hypotheses used. Lose-stay errors were committed with greater frequency among patients with frontal lobe lesions, although not all subjects with frontal lobe tumors exhibited this error tendency. The results of hypothesis sampling and a second visual discrimination transfer task suggested that the frontal lobe deficit was related to difficulty in attending to multiple cues and in monitoring feedback to segregate relevant from irrelevant sources of information.

Intrahemispheric localization of drawing dysfunction.

We evaluated drawing disability in 37 patients with right hemispheric stroke and in eight controls with no brain disease. Blinded evaluations included measures of overall recognizability and hemineglect. By mapping the CT lesions of patients, we found that damage to parieto-occipital cortex in poor drawers correlated with poor performance on a line bisection task whereas frontal, subcortical damage in poor drawers did not. We propose that drawing disability may be produced by visual-spatial dysfunction in patients with posterior lesions and by a disturbance of integrated motor function in those with frontal, subcortical damage.

Interhemispheric transfer of language in patients with left frontal cerebral arteriovenous malformation.

Cerebral arteriovenous malformations (AVMs) are frequently evaluated before therapeutic embolization by superselective injection of anesthetics into individual arterial branches so as to determine whether permanent occlusion would affect eloquent function. In Experiment 1, we used this adaptation of the Wada procedure to study three right-handed adult patients with left frontal cerebral AVMs by injecting vessels in Wernicke's and Broca's areas, respectively, and assessing language functions. The results showed that superselective testing in the inferior division of the left MCA in all three patients produced a dense Wernicke's aphasia. Injections into the left frontal regions, however, resulted in right paresis in all patients, but no language deficits including no loss of fluency. In Experiment 2, Patient 2 underwent fMRI activation for spontaneous word-list generation using multi-slice echo planar BOLD techniques at 1.5 Tesla. A voxel-by-voxel comparison of rest vs activation for each task was performed with a Z-score threshold of 2.5 SD for activated voxels. There was activation in the right hemisphere in the insula, frontal operculum pars opercularis, and inferior frontal gyrus, an area homologous to Broca's area in the left hemisphere. There was also activation in the left hemisphere in the Rolandic region, but language function was unaffected during Wada testing in this area. These data suggested that features of expressive language were no longer controlled by the left frontal lobe where the AVM was located, and provided new evidence for interhemispheric re-organization under conditions of chronic neurovascular disease.