The visual cortex and visual cognition in Huntington's disease: An overview of current literature.

The processing of visual stimuli from retina to higher cortical areas has been extensively studied in the human brain. In Huntington's disease (HD), an inherited neurodegenerative disorder, it is suggested that visual processing deficits are present in addition to more characteristic signs such as motor disturbances, cognitive dysfunction, and behavioral changes. Visual deficits are clinically important because they influence overall cognitive performance and have implications for daily functioning. The aim of this review is to summarize current literature on clinical visual deficits, visual cognitive impairment, and underlying visual cortical changes in HD patients. A literature search was conducted using the electronic database of PubMed/Medline. This review shows that changes of the visual system in patients with HD were not the primary focus of currently published studies. Still, early atrophy and alterations of the posterior cerebral cortex was frequently observed, primarily in the associative visual cortical areas such as the lingual and fusiform gyri, and lateral occipital cortex. Changes were even present in the premanifest phase, before clinical onset of motor symptoms, suggesting a primary region for cortical degeneration in HD. Although impairments in visuospatial processing and visual perception were reported in early disease stages, heterogeneous cognitive batteries were used, making a direct comparison between studies difficult. The use of a standardized battery of visual cognitive tasks might therefore provide more detailed information regarding the extent of impairments in specific visual domains. Further research could provide more insight into clinical, functional, and pathophysiological changes of the visual pathway in HD.

The perisylvian language network and language analytical abilities.

Aiming at exploring the brain's structural organisation underlying successful second language learning, we investigate the anatomy of the perisylvian language network in a group of healthy adults, consisting of participants with high and average language analytical abilities. Utilising deterministic tractography, six tracts per participant (left and right long direct segment, left and right indirect anterior segment and left and right indirect posterior segment) were virtually dissected and measurements pertaining to their microstructural organisation were collected. Our results obtained by means of linear discriminant analysis pointed to mean diffusivity (MD) values of three tracts (right anterior, left long and left anterior segments) as best discriminating between the two groups. By far the highest coefficient was obtained for the MD values of the right anterior segment, pointing to the role of the right white matter fronto-parietal connectivity for superior language learning abilities. The results imply the importance of attentional processes and reasoning abilities for successful L2 acquisition, and support previous findings concerning right-hemispheric involvement in language learning.

In vivo visualization of the locus coeruleus in humans: quantifying the test-retest reliability.

The locus coeruleus (LC) is a brainstem nucleus involved in important cognitive functions. Recent developments in neuroimaging methods and scanning protocols have made it possible to visualize the human LC in vivo by utilizing a T1-weighted turbo spin echo (TSE) scan. Despite its frequent use and its application as a biomarker for tracking the progress of monoaminergic-related neurodegenerative diseases, no study to date has investigated the reproducibility and inter-observer variability of LC identification using this TSE scan sequence. In this paper, we aim to quantify the test-retest reliability of LC imaging by assessing stability of the TSE contrast of the LC across two independent scan sessions and by quantifying the intra- and inter-rater reliability of the TSE scan. Additionally, we created a probabilistic LC atlas which can facilitate the spatial localization of the LC in standardized (MNI) space. Seventeen healthy volunteers participated in two scanning sessions with a mean intersession interval of 2.8 months. We found that for intra-rater reliability the mean Dice coefficient ranged between 0.65 and 0.74, and inter-rater reliability ranged between 0.54 and 0.64, showing moderate reproducibility. The mean LC contrast was 13.9% (SD 3.8) and showed scan-rescan stability (ROI approach: ICC = 0.63; maximum intensity approach: ICC = 0.53). We conclude that localization and segmentation of the LC in vivo are a challenging but reliable enterprise although clinical or longitudinal studies should be carried out carefully.

New insights in the neuroanatomy of the human adult superior hypogastric plexus and hypogastric nerves.

BACKGROUND: The superior hypogastric plexus (SHP) is an autonomic plexus, located ventrally to the abdominal aorta and its bifurcation, innervating pelvic viscera. It is classically described as being composed of merely sympathetic fibres. However, post-operative complications after surgery damaging the peri-aortic retroperitoneal compartment suggest the existence of parasympathetic fibres. This immunohistochemical study describes the neuroanatomical composition of the human mature SHP. MATERIAL AND METHODS: Eight pre-determined retroperitoneal localizations including the lumbar splanchnic nerves, the SHP and the HN were studied in four human cadavers. Control tissues (white rami, grey rami, vagus nerve, splanchnic nerves, sympathetic ganglia, sympathetic chain and spinal nerve) were collected to verify the results. All tissues were stained with haematoxylin and eosin and antibodies S100, tyrosine hydroxylase (TH), vasoactive intestinal peptide (VIP) and myelin basic protein (MBP) to identify pre- and postganglionic parasympathetic and sympathetic nerve fibres. RESULTS: All tissues comprising the SHP and hypogastric nerves (HN) showed isolated expression of TH, VIP and MBP, revealing the presence of three types of fibres: postganglionic adrenergic sympathetic fibres marked by TH, unmyelinated VIP-positive fibres and myelinated preganglionic fibres marked by MBP. Analysis of control tissues confirmed that TH, VIP and MBP were well usable to interpret the neurochemical composition of the SHP and HN. CONCLUSION: The human SHP and HN contain sympathetic and most likely postganglionic parasympathetic fibres. The origin of these fibres is still to be elucidated, however surgical damage in the peri-aortic retroperitoneal compartment may cause pelvic organ dysfunction related to both parasympathetic and sympathetic denervation.

Three-dimensional inversion recovery manganese-enhanced MRI of mouse brain using super-resolution reconstruction to visualize nuclei involved in higher brain function.

The visualization of activity in mouse brain using inversion recovery spin echo (IR-SE) manganese-enhanced MRI (MEMRI) provides unique contrast, but suffers from poor resolution in the slice-encoding direction. Super-resolution reconstruction (SRR) is a resolution-enhancing post-processing technique in which multiple low-resolution slice stacks are combined into a single volume of high isotropic resolution using computational methods. In this study, we investigated, first, whether SRR can improve the three-dimensional resolution of IR-SE MEMRI in the slice selection direction, whilst maintaining or improving the contrast-to-noise ratio of the two-dimensional slice stacks. Second, the contrast-to-noise ratio of SRR IR-SE MEMRI was compared with a conventional three-dimensional gradient echo (GE) acquisition. Quantitative experiments were performed on a phantom containing compartments of various manganese concentrations. The results showed that, with comparable scan times, the signal-to-noise ratio of three-dimensional GE acquisition is higher than that of SRR IR-SE MEMRI. However, the contrast-to-noise ratio between different compartments can be superior with SRR IR-SE MEMRI, depending on the chosen inversion time. In vivo experiments were performed in mice receiving manganese using an implanted osmotic pump. The results showed that SRR works well as a resolution-enhancing technique in IR-SE MEMRI experiments. In addition, the SRR image also shows a number of brain structures that are more clearly discernible from the surrounding tissues than in three-dimensional GE acquisition, including a number of nuclei with specific higher brain functions, such as memory, stress, anxiety and reward behavior.

Foot orgasm syndrome: a case report in a woman.

INTRODUCTION: Spontaneous orgasm triggered from inside the foot has so far not been reported in medical literature. AIMS: The study aims to report orgasmic feelings in the left foot of a woman. METHODS: A woman presented with complaints of undesired orgasmic sensations originating in her left foot. In-depth interview, physical examination, sensory testing, magnetic resonance imaging (MRI-scan), electromyography (EMG), transcutaneous electrical nerve stimulation (TENS), and blockade of the left S1 dorsal root ganglion were performed. MAIN OUTCOME MEASURES: The main outcomes are description of this clinical syndrome, results of TENS application, and S1 dorsal root ganglion blockade. RESULTS: Subtle attenuation of sensory amplitudes of the left suralis, and the left medial and lateral plantar nerve tracts was found at EMG. MRI-scan disclosed no foot abnormalities. TENS at the left metatarso-phalangeal joint-III of the left foot elicited an instant orgasmic sensation that radiated from plantar toward the vagina. TENS applied to the left side of the vagina elicited an orgasm that radiated to the left foot. Diagnostic blockade of the left S1 dorsal root ganglion with 0.8 mL bupivacaine 0.25 mg attenuated the frequency and intensity of orgasmic sensation in the left foot with 50% and 80%, respectively. Additional therapeutic blockade of the same ganglion with 0.8 mL bupivacaine 0.50 mg combined with pulsed radiofrequency treatment resulted in a complete disappearance of the foot-induced orgasmic sensations. CONCLUSION: Foot orgasm syndrome (FOS) is descibed in a woman. Blockade of the left S1 dorsal root ganglion alleviated FOS. It is hypothesized that FOS, occurring 1.5 years after an intensive care emergency, was caused by partial nerve regeneration (axonotmesis), after which afferent (C-fiber) information from a small reinnervated skin area of the left foot and afferent somatic and autonomous (visceral) information from the vagina on at least S1 spinal level is misinterpreted by the brain as being solely information originating from the vagina.

Decreased expression of mineralocorticoid receptor mRNA and its splice variants in postmortem brain regions of patients with major depressive disorder.

Appropriate signaling in the brain by the glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) is critical in regulation of the hypothalamic-pituitary-adrenal (HPA) axis, emotional arousal and cognitive performance. To date, few data exist on MR (and GR) expression in the brain of patients suffering from major depressive disorder (MDD). With the help of quantitative PCR we assessed MR and GR mRNA expression, including the splice variants MRα and MRß, in tissue samples from the hippocampus, amygdala, inferior frontal gyrus, cingulate gyrus and nucleus accumbens. Expression levels were compared between tissue samples from six MDD patients and six non-depressed subjects. Relative to total GR, total MR mRNA expression was higher in hippocampus and lower in the amygdala, inferior frontal gyrus and nucleus accumbens. Both MRα and MRß could be detected in all brain regions that were analyzed, although MRß expression was low. Significantly lower expression levels (30-50%) were detected for MR or GR in hippocampal, inferior frontal gyrus and cingulate gyrus tissue from MDD patients (p < .05), while no differences were found in the amygdala or nucleus accumbens. The data show that both MRα and MRß mRNA are expressed throughout the human limbic brain with highest expressions in the hippocampus. A decreased expression of corticosteroid receptors in specific brain regions of MDD patients could underlie HPA hyperactivity, mood and cognitive disturbances often observed in patients suffering from stress-related psychopathologies.

Type grouping in rat skeletal muscle after crush injury.

OBJECT: Accuracy of reinnervation is an important factor that determines outcome after nerve injury and repair. Type grouping--the clustering of muscle fibers of the same type after reinnervation--can be used to investigate the accuracy of reinnervation. In this study, the degree of type grouping after crush injury in rats was compared with the clustering of muscle fibers after autografting or single-lumen nerve grafting. METHODS: Twelve weeks after sciatic nerve crush injury in rats, clustering of Type I muscle fibers was analyzed in the target muscle with adenosine 5'-triphosphatase staining. In addition, the number of regenerated axons was determined in the nerve distal to the crush injury. Results were compared with that of the authors' previous study. RESULTS: Type grouping was more abundant after crush injury than after autograft or single-lumen nerve graft repair. CONCLUSIONS: Crush injury leads to more clustered innervation of muscle fibers, probably because the Schwann cell basal lamina tubes are not interrupted as they are in autograft or artificial nerve graft repair. This finding adds to understanding the processes playing a role in nerve regeneration.

Differential expression of glucocorticoid receptor transcripts in major depressive disorder is not epigenetically programmed.

Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis is one of the most consistent findings in major depressive disorder (MDD). Impaired HPA feedback may be due to the lower glucocorticoid receptor (GR) or mineralocorticoid receptor (MR) levels in the forebrain. GR levels are transcriptionally controlled by multiple untranslated alternative first exons, each with its own promoter providing a mechanism for tissue-specific fine-tuning of GR levels. Recently epigenetic methylation of these GR promoters was shown to modulate hippocampal GR levels. Here we investigate in post-mortem brain tissues whether in MDD HPA axis hyperactivity may be due to epigenetic modulation of GR transcript variants. Levels of GRalpha, GRbeta and GR-P transcripts were homogeneous throughout the limbic system, with GRalpha being the most abundant (83%), followed by GR-P (5-6%) while GRbeta was barely detectable (0.02%). Among the alternative first exons, 1B and 1C were the most active, while 1E and 1J showed the lowest expression and transcript 1F expressed intermediate levels of about 1%. In MDD, total GR levels were unaltered, although GRalpha was decreased in the amygdala and cingulate gyrus (p<0.05); transcripts containing exons 1B, 1C and 1F were lower, and 1D and1J were increased in some regions. NGFI-A, a transcription factor of exon 1F was down-regulated in the hippocampus of MDD patients; concomitantly exon 1F expression was reduced. Bisulphite sequencing of the alternative promoters showed low methylation levels in both MDD and control brains. Promoter 1F was uniformly unmethylated, suggesting that reduced 1F transcript levels are not linked to promoter methylation but to the observed dearth of NGFI-A. Previous studies showed high methylation levels in the 1F promoter, associated with childhood abuse. Provided our donors were not abused, our results suggest that the pathomechanism of MDD is similar but nevertheless distinct from that of abuse victims, explaining the clinical similarity of both conditions and that susceptibility to depression may be either predisposed by early trauma or developed independent of such a condition. However, this should be further confirmed in dedicated studies in larger cohorts.

The subthalamic nucleus. Part I: development, cytology, topography and connections.

This monograph (Part I of two volumes) on the subthalamic nucleus (STN) accentuates the gap between experimental animal and human information concerning subthalamic development, cytology, topography and connections. The light and electron microscopical cytology focuses on the open nucleus concept and the neuronal types present in the STN. The cytochemistry encompasses enzymes, NO, glial fibrillary acidic protein (GFAP), calcium binding proteins, and receptors (dopamine, cannabinoid, opioid, glutamate, gamma-aminobutyric acid (GABA), serotonin, cholinergic, and calcium channels). The ontogeny of the subthalamic cell cord is also reviewed. The topography concerns the rat, cat, baboon and human STN. The descriptions of the connections are also given from a historical point of view. Recent tracer studies on the rat nigro-subthalamic connection revealed contralateral projections. Part II of the two volumes (volume 199) on the subthalamic nucleus (STN) starts with a systemic model of the basal ganglia to evaluate the position of the STN in the direct, indirect and hyperdirect pathways. A summary of in vitro studies is given, describing STN spontaneous activity as well as responses to depolarizing and hyperpolarizing inputs and high-frequency stimulation. STN bursting activity and the underlying ionic mechanisms are investigated. Deep brain stimulation used for symptomatic treatment of Parkinson's disease is discussed in terms of the elements that are influenced and its hypothesized mechanisms. This part of the monograph explores the pedunculopontine-subthalamic connections and summarizes attempts to mimic neurotransmitter actions of the pedunculopontine nucleus in cell cultures and high-frequency stimulation on cultured dissociated rat subthalamic neurons. STN cell models--single- and multi-compartment models and system-level models are discussed in relation to subthalamic function and dysfunction. Parts I and II are compared.

Effect of nerve graft porosity on the refractory period of regenerating nerve fibers.

OBJECT: In the present study the authors consider the influence of the porosity of synthetic nerve grafts on peripheral nerve regeneration. METHODS: Microporous (1-13 microm) and nonporous nerve grafts made of a copolymer of trimethylene carbonate and epsilon-caprolactone were tested in an animal model. Twelve weeks after surgery, nerve and muscle morphological and electrophysiological results of regenerated nerves that had grown through the synthetic nerve grafts were compared with autografted and untreated (control) sciatic nerves. Based on the observed changes in the number and diameter of the nerve fibers, the predicted values of the electrophysiological parameters were calculated. RESULTS: The values of the morphometric parameters of the peroneal nerves and the gastrocnemius and anterior tibial muscles were similar if not equal in the rats receiving synthetic nerve grafts. The refractory periods, however, were shorter in porous compared with nonporous grafted nerves, and thus were closer to control values. CONCLUSIONS: A shorter refractory period enables the axon to follow the firing frequency of the neuron more effectively and allows a more adequate target organ stimulation. Therefore, porous are preferred over nonporous nerve grafts.

Electrophysiology and morphometry of the Aalpha- and Abeta-fiber populations in the normal and regenerating rat sciatic nerve.

We studied electrophysiological and morphological properties of the Aalpha- and Abeta-fibers in the regenerating sciatic nerve to establish whether these fiber types regenerate in numerical proportion and whether and how the electrophysiological properties of these fiber types are adjusted during regeneration. Compound action potentials were evoked from isolated sciatic nerves 12 weeks after autografting. Nerve fibers were gradually recruited either by increasing the stimulus voltage from subthreshold to supramaximal levels or by increasing the interval between two supramaximal stimuli to obtain the cumulative distribution of the extracellular firing thresholds and refractory periods, respectively. Thus, the mean conduction velocity (MCV), the maximal charge displaced during the compound action potential (Q(max)), the mean firing threshold (V(50)), and the mean refractory period (t(50)) were determined. The number of myelinated nerve fibers and their fiber diameter frequency distributions were determined in the peroneal nerve. Mathematical modeling applied to fiber recruitment and diameter distributions allowed discrimination of the Aalpha- and Abeta-fiber populations. In regenerating nerves, the number of Aalpha-fibers increased fourfold while the number of Abeta-fibers did not change. In regenerating Aalpha- and Abeta-fibers, the fiber diameter decreased and V(50) and t(50) increased. The regenerating Aalpha-fibers' contribution to Q(max) decreased considerably while that of the Abeta-fibers remained the same. Correlation of the electrophysiological data to the morphological data provided indications that the ion channel composition of both the Aalpha- and Abeta-fibers are altered during regeneration. This demonstrates that combining morphometric and electrophysiological analysis provides better insight in the changes that occur during regeneration.

Adhesion and growth of human Schwann cells on trimethylene carbonate (co)polymers.

Seeding of artificial nerve grafts with Schwann cells is a promising strategy for bridging large nerve defects. The aim of the present study was to evaluate the adhesion and growth of human Schwann cells (HSCs) on 1,3-trimethylene carbonate (TMC) and epsilon-caprolactone copolymers, with the final goal of using these materials in the development of an artificial nerve graft. The adhesion, proliferation, and morphology of HSCs on copolymers containing 10 and 82 mol % of TMC and on the parent homopolymers were investigated. HSCs adhered faster and in greater numbers on the copolymer with 82 mol % of TMC and on the TMC homopolymer compared with the other (co)polymers. On all polymer films, cell adhesion was lower than on gelatin (positive control). Despite differences in cell adhesion, cells displayed exponential growth on all tested surfaces, with similar growth rates. Cell numbers doubled approximately every 3 days on all substrates. When the polymer films were coated with fibronectin, no significant differences in cell adhesion and proliferation were observed between coated polymer surfaces and gelatin. The results indicate that all tested materials support the adhesion and proliferation of HSCs and can in principle be used for the preparation of flexible and slowly degrading nerve guides.

Repair of ventral root avulsions of the brachial plexus: a review.

Traumatic root avulsions of the brachial plexus constitute a devastating lesion resulting in loss of function of the upper limb and carry a large emotional and socioeconomic impact. In this literature survey, the different factors involved in root avulsion are discussed in combination with various surgical techniques for repair of experimental ventral root avulsion. Until now repair of root avulsions did not generate unequivocal proof of recovery of limb function, particularly of the hand. More experimental studies are needed to assess the efficacy of several repair techniques, the optimal timing for surgery, and the complications associated with spinal cord manipulation.