129,347 research outputs found
Music and the brain: disorders of musical listening
No full textThe study of the brain bases for normal musical listening has advanced greatly in the last 30 years. The evidence from basic and clinical neuroscience suggests that listening to music involves many cognitive components with distinct brain substrates. Using patient cases reported in the literature, we develop an approach for understanding disordered musical listening that is based on the systematic assessment of the perceptual and cognitive analysis of music and its emotional effect. This approach can be applied both to acquired and congenital deficits of musical listening, and to aberrant listening in patients with musical hallucinations. Both the bases for normal musical listening and the clinical assessment of disorders now have a solid grounding in systems neuroscience
A Study of Brain Networks Associated with Swallowing Using Graph-Theoretical Approaches
Full text linkFunctional connectivity between brain regions during swallowing tasks is still not well understood. Understanding these complex interactions is of great interest from both a scientific and a clinical perspective. In this study, functional magnetic resonance imaging (fMRI) was utilized to study brain functional networks during voluntary saliva swallowing in twenty-two adult healthy subjects (all females, 23.1±1.52 years of age). To construct these functional connections, we computed mean partial correlation matrices over ninety brain regions for each participant. Two regions were determined to be functionally connected if their correlation was above a certain threshold. These correlation matrices were then analyzed using graph-theoretical approaches. In particular, we considered several network measures for the whole brain and for swallowing-related brain regions. The results have shown that significant pairwise functional connections were, mostly, either local and intra-hemispheric or symmetrically inter-hemispheric. Furthermore, we showed that all human brain functional network, although varying in some degree, had typical small-world properties as compared to regular networks and random networks. These properties allow information transfer within the network at a relatively high efficiency. Swallowing-related brain regions also had higher values for some of the network measures in comparison to when these measures were calculated for the whole brain. The current results warrant further investigation of graph-theoretical approaches as a potential tool for understanding the neural basis of dysphagia. © 2013 Luan et al
White matter damage and cognitive impairment after traumatic brain injury
No full textWhite matter disruption is an important determinant of cognitive impairment after brain injury, but conventional neuroimaging underestimates its extent. In contrast, diffusion tensor imaging provides a validated and sensitive way of identifying the impact of axonal injury. The relationship between cognitive impairment after traumatic brain injury and white matter damage is likely to
be complex. We applied a flexible technique—tract-based spatial statistics—to explore whether damage to specific white matter tracts is associated with particular patterns of cognitive impairment. The commonly affected domains of memory, executive function and information processing speed were investigated in 28 patients in the post-acute / chronic phase following traumatic brain injury and in 26 age-matched controls. Analysis of fractional anisotropy and diffusivity maps revealed widespread differences
in white matter integrity between the groups. Patients showed large areas of reduced fractional anisotropy, as well as increased mean and axial diffusivities, compared with controls, despite the small amounts of cortical and white matter damage visible on standard imaging. A stratified analysis based on the presence or absence of microbleeds (a marker of diffuse axonal injury) revealed diffusion tensor imaging to be more sensitive than gradient-echo imaging to white matter damage. The location of white matter abnormality predicted cognitive function to some extent. The structure of the fornices was correlated with associative learning and memory across both patient and control groups, whilst the structure of frontal lobe connections showed relationships with executive function that differed in the two groups. These results highlight the complexity of the relationships
between white matter structure and cognition. Although widespread and, sometimes, chronic abnormalities of white matter are identifiable following traumatic brain injury, the impact of these changes on cognitive function is likely to depend on damage to key pathways that link nodes in the distributed brain networks supporting high-level cognitive functions
Fabrication and use of D-serine biosensors for characterising D-serine signalling in rat brain
Full text linkD-serine is a co-agonist at NMDA receptors in the brain but the study of this amino
acid is restricted by current techniques. I have designed highly sensitive D-serine
biosensors that permit accurate real-time recordings of D-serine in the brain in a
selective manner. I demonstrate that these tools are ideal for investigating factors
involved in the regulation of this amino acid and the role that D-serine plays in
excitotoxic cell death mediated via NMDA receptors.
I have established that the extracellular basal concentrations of D-serine in the rat
brain are heterogeneous and vary even within brain structures. This suggests that Dserine
is an important regulatory constraint for NMDA receptor activation, as
receptor response can only be potentiated in regions with low D-serine content.
Additionally, I show that these microelectrode biosensors have the potential to be
used in vivo to detected extracellular D-serine levels.
In addition I have observed real-time activity dependent regulation (both loss and
release) of D-serine by ionotropic glutamate receptor agonists AMPA, NMDA and
kainate, PAR1-agonist TFFLLRNH2 and high frequency stimulation in vitro in a
number of brain areas. A decrease in D-serine concentration is potentially
neuroprotective as it suggests a reduction in NMDA receptor activation. However,
D-serine release can be observed in regions where the co-agonist site of the NMDA
receptor is likely to be already saturated implying an alternative function of D-serine
in the brain. These findings indicate multifaceted regulation of this amino acid that is
brain-region specific.
Finally, I have investigated the role of D-serine release during models of stroke
(hypoxia and ischemia) and found that D-serine levels are reduced in brain regions
deprived of oxygen. This is ultimately neuroprotective as it will reduce over -
excitation at the NMDA receptor during these insults. In the more profound model of
stroke, oxygen-glucose deprivation, D-serine is eventually released. This release
precedes anoxic depolarisation and could therefore contribute to its initiation via
enhanced activation of the NMDA receptor
Phase dependent modulation of tremor amplitude in essential tremor through thalamic stimulation
Full text linkHigh frequency deep brain stimulation of the thalamus can help ameliorate severe essential tremor. Here we explore how the efficacy, efficiency and selectivity of thalamic deep brain stimulation might be improved in this condition. We started from the hypothesis that the effects of electrical stimulation on essential tremor may be phase dependent, and that, in particular, there are tremor phases at which stimuli preferentially lead to a reduction in the amplitude of tremor. The latter could be exploited to improve deep brain stimulation, particularly if tremor suppression could be reinforced by cumulative effects. Accordingly, we stimulated 10 patients with essential tremor and thalamic electrodes, while recording tremor amplitude and phase. Stimulation near the postural tremor frequency entrained tremor. Tremor amplitude was also modulated depending on the phase at which stimulation pulses were delivered in the tremor cycle. Stimuli in one half of the tremor cycle reduced median tremor amplitude by ∼10%, while those in the opposite half of the tremor cycle increased tremor amplitude by a similar amount. At optimal phase alignment tremor suppression reached 27%. Moreover, tremor amplitude showed a non-linear increase in the degree of suppression with successive stimuli; tremor suppression was increased threefold if a stimulus was preceded by four stimuli with a similar phase relationship with respect to the tremor, suggesting cumulative, possibly plastic, effects. The present results pave the way for a stimulation system that tracks tremor phase to control when deep brain stimulation pulses are delivered to treat essential tremor. This would allow treatment effects to be maximized by focussing stimulation on the optimal phase for suppression and by ensuring that this is repeated over many cycles so as to harness cumulative effects. Such a system might potentially achieve tremor control with far less power demand and greater specificity than current high frequency stimulation approaches, and may lower the risk for tolerance and rebound
Amyloid tracers detect multple binding sites in Alzheimer´s disease brain tissue.
Full text linkImaging fibrillar amyloid-β deposition in the human brain in vivo by positron emission tomography has improved our understanding of the time course of amyloid-β pathology in Alzheimer’s disease. The most widely used amyloid-β imaging tracer so far is 11C-Pittsburgh compound B, a thioflavin derivative but other 11C- and 18F-labelled amyloid-β tracers have been studied in patients with Alzheimer's disease and cognitively normal control subjects. However, it has not yet been established whether different amyloid tracers bind to identical sites on amyloid-β fibrils, offering the same ability to detect the regional amyloid-β burden in the brains. In this study, we characterized 3H-Pittsburgh compound B binding in autopsied brain regions from 23 patients with Alzheimer's disease and 20 control subjects (aged 50 to 88 years). The binding properties of the amyloid tracers FDDNP, AV-45, AV-1 and BF-227 were also compared with those of 3H-Pittsburgh compound B in the frontal cortices of patients with Alzheimer's disease. Saturation binding studies revealed the presence of high- and low-affinity 3H-Pittsburgh compound B binding sites in the frontal cortex (Kd1: 3.5 ± 1.6 nM; Kd2: 133 ± 30 nM) and hippocampus (Kd1:5.6 ± 2.2 nM; Kd2: 181 ± 132 nM) of Alzheimer's disease brains. The relative proportion of high-affinity to low-affinity sites was 6:1 in the frontal cortex and 3:1 in the hippocampus. One control showed both high- and low-affinity 3H-Pittsburgh compound B binding sites (Kd1: 1.6 nM; Kd2: 330 nM) in the cortex while the others only had a low-affinity site (Kd2: 191 ± 70 nM). 3H-Pittsburgh compound B binding in Alzheimer's disease brains was higher in the frontal and parietal cortices than in the caudate nucleus and hippocampus, and negligible in the cerebellum. Competitive binding studies with 3H-Pittsburgh compound B in the frontal cortices of Alzheimer's disease brains revealed high- and low-affinity binding sites for BTA-1 (Ki: 0.2 nM, 70 nM), florbetapir (1.8 nM, 53 nM) and florbetaben (1.0 nM, 65 nM). BF-227 displaced 83% of 3H-Pittsburgh compound B binding, mainly at a low-affinity site (311 nM), whereas FDDNP only partly displaced (40%). We propose a multiple binding site model for the amyloid tracers (binding sites 1, 2 and 3), where AV-45 (florbetapir), AV-1 (florbetaben), and Pittsburgh compound B, all show nanomolar affinity for the high-affinity site (binding site 1), as visualized by positron emission tomography. BF-227 shows mainly binding to site 3 and FDDNP shows only some binding to site 2. Different amyloid tracers may provide new insight into the pathophysiological mechanisms in the progression of Alzheimer’s disease
Intonation processing in congenital amusia: discrimination, identification and imitation
No full textThis study investigated whether congenital amusia, a neuro-developmental disorder of musical perception, also has implications for speech intonation processing. In total, 16 British amusics and 16 matched controls completed five intonation perception tasks and two pitch threshold tasks. Compared with controls, amusics showed impaired performance on discrimination, identification and imitation of statements and questions that were characterized primarily by pitch direction differences in the final word. This intonation-processing deficit in amusia was largely associated with a psychophysical pitch direction discrimination deficit. These findings suggest that amusia impacts upon one’s language abilities in subtle ways, and support previous evidence that pitch processing in language and music involves shared mechanisms
A Multivariate Surface-Based Analysis of the Putamen in Premature Newborns: Regional Differences within the Ventral Striatum
Full text linkMany children born preterm exhibit frontal executive dysfunction, behavioral problems including attentional deficit/hyperactivity disorder and attention related learning disabilities. Anomalies in regional specificity of cortico-striato-thalamo-cortical circuits may underlie deficits in these disorders. Nonspecific volumetric deficits of striatal structures have been documented in these subjects, but little is known about surface deformation in these structures. For the first time, here we found regional surface morphological differences in the preterm neonatal ventral striatum. We performed regional group comparisons of the surface anatomy of the striatum (putamen and globus pallidus) between 17 preterm and 19 term-born neonates at term-equivalent age. We reconstructed striatal surfaces from manually segmented brain magnetic resonance images and analyzed them using our in-house conformal mapping program. All surfaces were registered to a template with a new surface fluid registration method. Vertex-based statistical comparisons between the two groups were performed via four methods: univariate and multivariate tensor-based morphometry, the commonly used medial axis distance, and a combination of the last two statistics. We found statistically significant differences in regional morphology between the two groups that are consistent across statistics, but more extensive for multivariate measures. Differences were localized to the ventral aspect of the striatum. In particular, we found abnormalities in the preterm anterior/inferior putamen, which is interconnected with the medial orbital/prefrontal cortex and the midline thalamic nuclei including the medial dorsal nucleus and pulvinar. These findings support the hypothesis that the ventral striatum is vulnerable, within the cortico-stiato-thalamo-cortical neural circuitry, which may underlie the risk for long-term development of frontal executive dysfunction, attention deficit hyperactivity disorder and attention-related learning disabilities in preterm neonates. © 2013 Shi et al
Morphologic and functional correlates of synaptic pathology in the cathepsin D knockout mouse model of congenital neuronal ceroid lipofuscinosis
Full text linkMutations in the cathepsin D (CTSD) gene cause an aggressive neurodegenerative disease (congenital neuronal ceroid lipofuscinosis) that leads to early death. Recent evidence suggests that presynaptic abnormalities play a major role in the pathogenesis of CTSD deficiencies. To identify the early events that lead to synaptic alterations, we investigated synaptic ultrastructure and function in presymptomatic CTSD knockout (Ctsd) mice. Electron microscopy revealed that there were significantly greater numbers of readily releasable synaptic vesicles present in Ctsd mice than in wild-type control mice as early as postnatal day 16. The size of this synaptic vesicle pool continued to increase with disease progression in the hippocampus and thalamus of the Ctsd mice. Electrophysiology revealed a markedly decreased frequency of miniature excitatory postsynaptic currents (mEPSCs) with no effect on paired-pulse modulation of the evoked excitatory post synaptic potentials in the hippocampus of Ctsd mice. The reduced mEPSCs frequency was observed before the appearance of epilepsy or any morphologic sign of synaptic degeneration. Taken together, these data indicate that CTSD is required for normal synaptic function and that a failure in synaptic trafficking or recycling may bean early and important pathologic mechanism in Ctsd mice; these presynaptic abnormalities may initiate synaptic degeneration in advance of subsequent neuronal loss
N-methyl-D-aspartate antibody encephalitis: temporal progression of clinical and paraclinical observations in a predominantly non-paraneoplastic disorder of both sexes
Full text linkAntibodies to the N-methyl-d-aspartate subtype of glutamate receptor have been associated with a newly-described encephalopathy that has been mainly identified in young females with ovarian tumours. However, the full clinical spectrum and treatment responses are not yet clear. We established a sensitive cell-based assay for detection of N-methyl-d-aspartate receptor antibodies in serum or cerebrospinal fluid, and a quantitative fluorescent immunoprecipitation assay for serial studies. Although there was marked intrathecal synthesis of N-methyl-d-aspartate receptor antibodies, the absolute levels of N-methyl-d-aspartate receptor antibodies were higher in serum than in cerebrospinal fluid. N-methyl-d-aspartate receptor antibodies were of the immunoglobulin G1 subclass and were able to activate complement on N-methyl d-aspartate receptor-expressing human embryonic kidney cells. From questionnaires returned on 44 N-methyl-d-aspartate receptor antibody-positive patients, we identified a high proportion without a detected tumour (35/44, 80%: follow-up 3.6-121 months, median 16 months). Among the latter were 15 adult females (43%), 10 adult males (29%) and 10 children (29%), with four in the first decade of life. Overall, there was a high proportion (29%) of non-Caucasians. Good clinical outcomes, as defined by reductions in modified Rankin scores, correlated with decreased N-methyl-d-aspartate receptor antibody levels and were associated with early (<40 days) administration of immunotherapies in non-paraneoplastic patients (P < 0.0001) and earlier tumour removal in paraneoplastic patients (P = 0.02). Ten patients (23%) who were first diagnosed during relapses had no evidence of tumours but had received minimal or no immunotherapy during earlier episodes. Temporal analysis of the onset of the neurological features suggested progression through two main stages. The time of onset of the early features, characterized by neuropsychiatric symptoms and seizures preceded by a median of 10-20 days, the onset of movement disorders, reduction in consciousness and dysautonomia. This temporal dichotomy was also seen in the timing of cerebrospinal fluid, electroencephalographic and in the rather infrequent cerebral imaging changes. Overall, our data support a model in which the early features are associated with cerebrospinal fluid lymphocytosis, and the later features with appearance of oligoclonal bands. The immunological events and neuronal mechanisms underlying these observations need to be explored further, but one possibility is that the early stage represents diffusion of serum antibodies into the cortical grey matter, whereas the later stage results from secondary expansion of the immunological repertoire within the intrathecal compartment acting on subcortical neurons. Four patients, who only had temporal lobe epilepsy without oligoclonal bands, may represent restriction to the first stag
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