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Sample records for re-expression reduces subcortical

  1. Backward Masking: Evidence of Reduced Subcortical Amygdala Engagement in Autism

    ERIC Educational Resources Information Center

    Hall, Geoffrey B. C.; West, C. Dianne; Szatmari, Peter

    2007-01-01

    Recent data suggest that subthreshold presentation of emotional information is relayed to the amygdala along subcortical pathways. We examined the effect of backward masked neutral and anxious faces on the social decisions of a group of high functioning children with autism ages 7-13 years and matched controls. Participants were asked to select…

  2. Dcx reexpression reduces subcortical band heterotopia and seizure threshold in an animal model of neuronal migration disorder.

    PubMed

    Manent, Jean-Bernard; Wang, Yu; Chang, Yoonjeung; Paramasivam, Murugan; LoTurco, Joseph J

    2009-01-01

    Disorders of neuronal migration can lead to malformations of the cerebral neocortex that greatly increase the risk of seizures. It remains untested whether malformations caused by disorders in neuronal migration can be reduced by reactivating cellular migration and whether such repair can decrease seizure risk. Here we show, in a rat model of subcortical band heterotopia (SBH) generated by in utero RNA interference of the Dcx gene, that aberrantly positioned neurons can be stimulated to migrate by reexpressing Dcx after birth. Restarting migration in this way both reduces neocortical malformations and restores neuronal patterning. We further find that the capacity to reduce SBH continues into early postnatal development. Moreover, intervention after birth reduces the convulsant-induced seizure threshold to a level similar to that in malformation-free controls. These results suggest that disorders of neuronal migration may be eventually treatable by reengaging developmental programs both to reduce the size of cortical malformations and to reduce seizure risk.

  3. Reduced frontal-subcortical white matter connectivity in association with suicidal ideation in major depressive disorder

    PubMed Central

    Myung, W; Han, C E; Fava, M; Mischoulon, D; Papakostas, G I; Heo, J-Y; Kim, K W; Kim, S T; Kim, D J H; Kim, D K; Seo, S W; Seong, J-K; Jeon, H J

    2016-01-01

    Major depressive disorder (MDD) and suicidal behavior have been associated with structural and functional changes in the brain. However, little is known regarding alterations of brain networks in MDD patients with suicidal ideation. We investigated whether or not MDD patients with suicidal ideation have different topological organizations of white matter networks compared with MDD patients without suicidal ideation. Participants consisted of 24 patients with MDD and suicidal ideation, 25 age- and gender-matched MDD patients without suicidal ideation and 31 healthy subjects. A network-based statistics (NBS) and a graph theoretical analysis were performed to assess differences in the inter-regional connectivity. Diffusion tensor imaging (DTI) was performed to assess topological changes according to suicidal ideation in MDD patients. The Scale for Suicide Ideation (SSI) and the Korean version of the Barrett Impulsiveness Scale (BIS) were used to assess the severity of suicidal ideation and impulsivity, respectively. Reduced structural connectivity in a characterized subnetwork was found in patients with MDD and suicidal ideation by utilizing NBS analysis. The subnetwork included the regions of the frontosubcortical circuits and the regions involved in executive function in the left hemisphere (rostral middle frontal, pallidum, superior parietal, frontal pole, caudate, putamen and thalamus). The graph theoretical analysis demonstrated that network measures of the left rostral middle frontal had a significant positive correlation with severity of SSI (r=0.59, P=0.02) and BIS (r=0.59, P=0.01). The total edge strength that was significantly associated with suicidal ideation did not differ between MDD patients without suicidal ideation and healthy subjects. Our findings suggest that the reduced frontosubcortical circuit of structural connectivity, which includes regions associated with executive function and impulsivity, appears to have a role in the emergence of suicidal

  4. Reduced frontal-subcortical white matter connectivity in association with suicidal ideation in major depressive disorder.

    PubMed

    Myung, W; Han, C E; Fava, M; Mischoulon, D; Papakostas, G I; Heo, J-Y; Kim, K W; Kim, S T; Kim, D J H; Kim, D K; Seo, S W; Seong, J-K; Jeon, H J

    2016-06-07

    Major depressive disorder (MDD) and suicidal behavior have been associated with structural and functional changes in the brain. However, little is known regarding alterations of brain networks in MDD patients with suicidal ideation. We investigated whether or not MDD patients with suicidal ideation have different topological organizations of white matter networks compared with MDD patients without suicidal ideation. Participants consisted of 24 patients with MDD and suicidal ideation, 25 age- and gender-matched MDD patients without suicidal ideation and 31 healthy subjects. A network-based statistics (NBS) and a graph theoretical analysis were performed to assess differences in the inter-regional connectivity. Diffusion tensor imaging (DTI) was performed to assess topological changes according to suicidal ideation in MDD patients. The Scale for Suicide Ideation (SSI) and the Korean version of the Barrett Impulsiveness Scale (BIS) were used to assess the severity of suicidal ideation and impulsivity, respectively. Reduced structural connectivity in a characterized subnetwork was found in patients with MDD and suicidal ideation by utilizing NBS analysis. The subnetwork included the regions of the frontosubcortical circuits and the regions involved in executive function in the left hemisphere (rostral middle frontal, pallidum, superior parietal, frontal pole, caudate, putamen and thalamus). The graph theoretical analysis demonstrated that network measures of the left rostral middle frontal had a significant positive correlation with severity of SSI (r=0.59, P=0.02) and BIS (r=0.59, P=0.01). The total edge strength that was significantly associated with suicidal ideation did not differ between MDD patients without suicidal ideation and healthy subjects. Our findings suggest that the reduced frontosubcortical circuit of structural connectivity, which includes regions associated with executive function and impulsivity, appears to have a role in the emergence of suicidal

  5. Reduced medial prefrontal-subcortical connectivity in dysphoria: Granger causality analyses of rapid functional magnetic resonance imaging.

    PubMed

    Sabatinelli, Dean; McTeague, Lisa M; Dhamala, Mukesh; Frank, David W; Wanger, Timothy J; Adhikari, Bhim M

    2015-02-01

    A cortico-limbic network consisting of the amygdala, medial prefrontal cortex (mPFC), and ventral striatum (vSTR) has been associated with altered function in emotional disorders. Here we used rapidly sampled functional magnetic resonance imaging and Granger causality analyses to assess the directional connectivity between these brain structures in a sample of healthy and age-matched participants endorsing moderate to severe depressive symptomatology as they viewed a series of natural scene stimuli varying systematically in pleasantness and arousal. Specifically during pleasant scene perception, dysphoric participants showed reduced activity in mPFC and vSTR, relative to healthy participants. In contrast, amygdala activity was enhanced to pleasant as well as unpleasant arousing scenes in both participant groups. Granger causality estimates of influence between mPFC and vSTR were significantly reduced in dysphoric relative to control participants during all picture contents. These findings provide direct evidence that during visual perception of evocative emotional stimuli, reduced reward-related activity in dysphoria is associated with dysfunctional causal connectivity between mPFC, amygdala, and vSTR.

  6. Oxidative mitochondrial DNA damage in peripheral blood mononuclear cells is associated with reduced volumes of hippocampus and subcortical gray matter in chronically HIV-infected patients

    PubMed Central

    Kallianpur, Kalpana J.; Gerschenson, Mariana; Mitchell, Brooks I.; LiButti, Daniel E.; Umaki, Tracie M.; Ndhlovu, Lishomwa C.; Nakamoto, Beau K.; Chow, Dominic C.; Shikuma, Cecilia M.

    2016-01-01

    Cross-sectional relationships were examined between regional brain volumes and mitochondrial DNA (mtDNA) 8-hydroxy-2-deoxyguanosine (8-oxo-dG) in peripheral blood mononuclear cells (PBMCs) of 47 HIV patients [mean age 51 years; 81% with HIV RNA ≤50 copies/mL] on combination antiretroviral therapy. The gene-specific DNA damage and repair assay measured mtDNA 8-oxo-dG break frequency. Magnetic resonance imaging was performed at 3 T. Higher mtDNA 8-oxo-dG was associated with lateral ventricular enlargement and with decreased volumes of hippocampus, pallidum, and total subcortical gray matter, suggesting the involvement of systemic mitochondrial-specific oxidative stress in chronic HIV-related structural brain changes and cognitive difficulties. Clarification of the mechanism may provide potential therapeutic targets. PMID:26923169

  7. The `subcortical dementia' of progressive supranuclear palsy

    PubMed Central

    Albert, Martin L.; Feldman, Robert G.; Willis, Anne L.

    1974-01-01

    Progressive supranuclear palsy (Steele et al.) has a characteristic pattern of dementia: (1) forgetfulness, (2) slowing of thought processes, (3) emotional or personality changes (apathy or depression with occasional outbursts of irritability), and (4) impaired ability to manipulate acquired knowledge. In many neurological disease states associated with subcortical pathology a similar pattern of dementia exists. The neurobehavioural changes of progressive supranuclear palsy thus typify a clinical pattern which may be referred to as subcortical dementia. The subcortical dementias have a striking clinical resemblance to the dementia which occurs after bifrontal lobe disease. However, the subcortical dementias can be clearly distinguished clinically from cortical dementias, other than frontal dementias. We propose as a tentative hypothesis that there may be common pathophysiological mechanisms underlying the subcortical dementias—in particular, disturbances of timing and activation. There are immediate practical implications of this hypothesis: drugs which have an effect on subcortical timing and activating mechanisms may be useful in the treatment of subcortical dementias. PMID:4819905

  8. Daily Physical Activity Is Associated with Subcortical Brain Volume and Cognition in Heart Failure.

    PubMed

    Alosco, Michael L; Brickman, Adam M; Spitznagel, Mary Beth; Sweet, Lawrence H; Josephson, Richard; Griffith, Erica Y; Narkhede, Atul; Hughes, Joel; Gunstad, John

    2015-11-01

    Cognitive impairment in heart failure (HF) is believed to in part stem from structural brain alterations, including shrinkage of subcortical regions. Fortunately, neurocognitive dysfunction in HF can be mitigated by physical activity (PA), though mechanisms for this phenomenon are unclear. PA is protective against age-related cognitive decline that may involve improved structural integrity to brain regions sensitive to aging (e.g., subcortical structures). Yet, no study has examined the benefits of PA on the brain in HF and we sought to do so and clarify related cognitive implications. Fifty older adults with HF completed a neuropsychological battery and wore an accelerometer for 7 days. All participants underwent brain MRI. This study targeted subcortical brain volume given subcortical alterations are often observed in HF and the sensitivity of PA to subcortical structures in other patient populations. Participants averaged 4348.49 (SD=2092.08) steps per day and greater daily steps predicted better attention/executive function, episodic memory, and language abilities, p's<.05. Medical and demographically adjusted regression analyses revealed higher daily steps per day predicted greater subcortical volume, with specific effects for the thalamus and ventral diencephalon, p's<.05. Greater subcortical volume was associated with better attention/executive function, p<.05. Higher daily PA was associated with increased subcortical brain volume and better cognition in older adults with HF. Longitudinal work is needed to clarify whether daily PA can attenuate brain atrophy in HF to reduce accelerated cognitive decline in this population.

  9. Subcortical processing in auditory communication.

    PubMed

    Pannese, Alessia; Grandjean, Didier; Frühholz, Sascha

    2015-10-01

    The voice is a rich source of information, which the human brain has evolved to decode and interpret. Empirical observations have shown that the human auditory system is especially sensitive to the human voice, and that activity within the voice-sensitive regions of the primary and secondary auditory cortex is modulated by the emotional quality of the vocal signal, and may therefore subserve, with frontal regions, the cognitive ability to correctly identify the speaker's affective state. So far, the network involved in the processing of vocal affect has been mainly characterised at the cortical level. However, anatomical and functional evidence suggests that acoustic information relevant to the affective quality of the auditory signal might be processed prior to the auditory cortex. Here we review the animal and human literature on the main subcortical structures along the auditory pathway, and propose a model whereby the distinction between different types of vocal affect in auditory communication begins at very early stages of auditory processing, and relies on the analysis of individual acoustic features of the sound signal. We further suggest that this early feature-based decoding occurs at a subcortical level along the ascending auditory pathway, and provides a preliminary coarse (but fast) characterisation of the affective quality of the auditory signal before the more refined (but slower) cortical processing is completed.

  10. Cortical deactivation induced by subcortical network dysfunction in limbic seizures

    PubMed Central

    Englot, Dario J.; Modi, Badri; Mishra, Asht M.; DeSalvo, Matthew; Hyder, Fahmeed; Blumenfeld, Hal

    2009-01-01

    Normal human consciousness may be impaired by two possible routes: direct reduced function in widespread cortical regions, or indirect disruption of subcortical activating systems. The route through which temporal lobe limbic seizures impair consciousness is not known. We recently developed an animal model which, like human limbic seizures, exhibits neocortical deactivation including cortical slow waves and reduced cortical cerebral blood flow (CBF). We now find through functional MRI (fMRI) that electrically-stimulated hippocampal seizures in rats cause increased activity in subcortical structures including the septal area and mediodorsal thalamus, along with reduced activity in frontal, cingulate, and retrosplenial cortex. Direct recordings from the hippocampus, septum, and medial thalamus demonstrated fast poly-spike activity associated with increased neuronal firing and CBF, while frontal cortex showed slow oscillations with decreased neuronal firing and CBF. Stimulation of septal area, but not hippocampus or medial thalamus, in the absence of a seizure resulted in cortical deactivation with slow oscillations and behavioral arrest, resembling changes seen during limbic seizures. Transecting the fornix, the major route from hippocampus to subcortical structures, abolished the negative cortical and behavioral effects of seizures. Cortical slow oscillations and behavioral arrest could be reconstituted in fornix-lesioned animals by inducing synchronous activity in the hippocampus and septal area, implying involvement of a downstream region converged upon by both structures. These findings suggest that limbic seizures may cause neocortical deactivation indirectly, through impaired subcortical function. If confirmed, subcortical networks may represent a target for therapies aimed at preserving consciousness in human temporal lobe seizures. PMID:19828814

  11. Subcortical control of precision grip after human spinal cord injury.

    PubMed

    Bunday, Karen L; Tazoe, Toshiki; Rothwell, John C; Perez, Monica A

    2014-05-21

    The motor cortex and the corticospinal system contribute to the control of a precision grip between the thumb and index finger. The involvement of subcortical pathways during human precision grip remains unclear. Using noninvasive cortical and cervicomedullary stimulation, we examined motor evoked potentials (MEPs) and the activity in intracortical and subcortical pathways targeting an intrinsic hand muscle when grasping a small (6 mm) cylinder between the thumb and index finger and during index finger abduction in uninjured humans and in patients with subcortical damage due to incomplete cervical spinal cord injury (SCI). We demonstrate that cortical and cervicomedullary MEP size was reduced during precision grip compared with index finger abduction in uninjured humans, but was unchanged in SCI patients. Regardless of whether cortical and cervicomedullary stimulation was used, suppression of the MEP was only evident 1-3 ms after its onset. Long-term (∼5 years) use of the GABAb receptor agonist baclofen by SCI patients reduced MEP size during precision grip to similar levels as uninjured humans. Index finger sensory function correlated with MEP size during precision grip in SCI patients. Intracortical inhibition decreased during precision grip and spinal motoneuron excitability remained unchanged in all groups. Our results demonstrate that the control of precision grip in humans involves premotoneuronal subcortical mechanisms, likely disynaptic or polysynaptic spinal pathways that are lacking after SCI and restored by long-term use of baclofen. We propose that spinal GABAb-ergic interneuronal circuits, which are sensitive to baclofen, are part of the subcortical premotoneuronal network shaping corticospinal output during human precision grip.

  12. [Phenylhexyl isothiocyanate induces gene p15 re-expression by regulating histone methylation and DNA demethylation in Molt-4 cells].

    PubMed

    Ma, Xu-Dong; Huang, Yi-Qun; Jiang, Shao-Hong; Zheng, Rui-Ji

    2010-06-01

    This study was aimed to investigate the regulatory effect of phenylhexyl isothiocyanate (PHI) on methylation of histone H3K4, H3K9 and demethylation of p15 gene in acute leukemia cell line Molt-4, and to explore the possible mechanism inducing re-expression of silent gene. The methylation status of histone H3K4, H3K9 and the expression of P15 protein in the Molt-4 cells treated with PHI were detected by Western blot; the methylation status of p15 gene in the Molt-4 cells before and after treatment with PHI was determined by methylation specific polymerase chain reaction (MSP); the expression level of p15 gene mRNA in Molt-4 cells treated with PHI was assayed by semiquantitative reverse transcription-PCR. The results indicated that the PHI could increase methylation of histone H3K4 and decrease methylation of histone H3K9 in concentration-and time-dependent manners. After treatment of Molt-4 cells with PHI for 5 days, the methylation of p15 gene was reduced, the significant hypermethylation of p15 gene was reversed, the silenced p15 gene re-expressed; the expressions of p15 mRNA and P15 protein were enhanced in concentration-dependent manner. It is concluded that probably through specifically regulating the methylation level of histone H3K4 and H3K9, the PHI causes the changes of chromosome space structure and results in the demethylation of CPG island in p15 gene, thereby induces the re-expression of p15 gene which was silenced.

  13. The Secondary Prevention of Small Subcortical Strokes (SPS3) study

    PubMed Central

    Benavente, Oscar R.; White, Carole L.; Pearce, Lesly; Pergola, Pablo; Roldan, Ana; Benavente, Marie-France; Coffey, Christopher; McClure, Leslie A.; Szychowski, Jeff M.; Conwit, Robin; Heberling, Patricia A.; Howard, George; Bazan, Carlos; Vidal-Pergola, Gabriela; Talbert, Robert; Hart, Robert G.

    2014-01-01

    Background Small subcortical strokes, also known as lacunar strokes, comprise more than 25% of brain infarcts, and the underlying vasculopathy is the most common cause of vascular cognitive impairment. How to optimally prevent stroke recurrence and cognitive decline in S3 patients is unclear. The aim of the Secondary Prevention of Small Subcortical Strokes study (Trial registration: NCT00059306) is to define strategies for reducing stroke recurrence, cognitive decline, and major vascular events. Methods Secondary Prevention of Small Subcortical Strokes is a randomised, multicentre clinical trial (n = 3000) being conducted in seven countries, and sponsored by the US NINDS/NIH. Patients with symptomatic small subcortical strokes in the six-months before and an eligible lesion on magnetic resonance imaging are simultaneously randomised, in a 2 × 2 factorial design, to antiplatelet therapy – 325 mg aspirin daily plus 75 mg clopidogrel daily, vs. 325 mg aspirin daily plus placebo, double-blind – and to one of two levels of systolic blood pressure targets –‘intensive’ (<130 mmHg) vs. ‘usual’ (130–149 mmHg). Participants are followed for an average of four-years. Time to recurrent stroke (ischaemic or haemorrhagic) is the primary outcome and will be analysed separately for each intervention. The secondary outcomes are the rate of cognitive decline and major vascular events. The primary and most secondary outcomes are adjudicated centrally by those unaware of treatment assignment. Conclusions Secondary Prevention of Small Subcortical Strokes will address several important clinical and scientific questions by testing two interventions in patients with recent magnetic resonance imaging-defined lacunar infarcts, which are likely due to small vessel disease. The results will inform the management of millions of patients with this common vascular disorder. PMID:21371282

  14. Subcortical functional reorganization due to early blindness.

    PubMed

    Coullon, Gaelle S L; Jiang, Fang; Fine, Ione; Watkins, Kate E; Bridge, Holly

    2015-04-01

    Lack of visual input early in life results in occipital cortical responses to auditory and tactile stimuli. However, it remains unclear whether cross-modal plasticity also occurs in subcortical pathways. With the use of functional magnetic resonance imaging, auditory responses were compared across individuals with congenital anophthalmia (absence of eyes), those with early onset (in the first few years of life) blindness, and normally sighted individuals. We find that the superior colliculus, a "visual" subcortical structure, is recruited by the auditory system in congenital and early onset blindness. Additionally, auditory subcortical responses to monaural stimuli were altered as a result of blindness. Specifically, responses in the auditory thalamus were equally strong to contralateral and ipsilateral stimulation in both groups of blind subjects, whereas sighted controls showed stronger responses to contralateral stimulation. These findings suggest that early blindness results in substantial reorganization of subcortical auditory responses.

  15. Subcortical amygdala pathways enable rapid face processing.

    PubMed

    Garvert, Mona M; Friston, Karl J; Dolan, Raymond J; Garrido, Marta I

    2014-11-15

    Human faces may signal relevant information and are therefore analysed rapidly and effectively by the brain. However, the precise mechanisms and pathways involved in rapid face processing are unclear. One view posits a role for a subcortical connection between early visual sensory regions and the amygdala, while an alternative account emphasises cortical mediation. To adjudicate between these functional architectures, we recorded magnetoencephalographic (MEG) evoked fields in human subjects to presentation of faces with varying emotional valence. Early brain activity was better explained by dynamic causal models containing a direct subcortical connection to the amygdala irrespective of emotional modulation. At longer latencies, models without a subcortical connection had comparable evidence. Hence, our results support the hypothesis that a subcortical pathway to the amygdala plays a role in rapid sensory processing of faces, in particular during early stimulus processing. This finding contributes to an understanding of the amygdala as a behavioural relevance detector.

  16. Subcortical infarction resulting in acquired stuttering.

    PubMed

    Ciabarra, A M; Elkind, M S; Roberts, J K; Marshall, R S

    2000-10-01

    Stuttering is an uncommon presentation of acute stroke. Reported cases have often been associated with left sided cortical lesions, aphasia, and difficulties with other non-linguistic tests of rhythmic motor control. Three patients with subcortical lesions resulting in stuttering are discussed. In one patient the ability to perform time estimations with a computerised repetitive time estimation task was characterised. One patient had a pontine infarct with clinical evidence of cerebellar dysfunction. A second patient had a left basal ganglionic infarct and a disruption of timing estimation. A third patient had a left subcortical infarct and a mild aphasia. These findings expand the reported distribution of infarction that can result in acquired stuttering. Subcortical mechanisms of speech control and timing may contribute to the pathophysiology of acquired stuttering.

  17. Hemispheric asymmetries in cortical and subcortical anatomy.

    PubMed

    Kang, Xiaojian; Herron, Timothy J; Ettlinger, Marc; Woods, David L

    2015-01-01

    Previous research studies have reported many hemispherical asymmetries in cortical and subcortical anatomy, but only a subset of findings is consistent across studies. Here, we used improved Freesurfer-based automated methods to analyse the properties of the cortex and seven subcortical structures in 138 young adult subjects. Male and female subjects showed similar hemispheric asymmetries in gyral and sulcal structures, with many areas associated with language processing enlarged in the left hemisphere (LH) and a number of areas associated with visuospatial processing enlarged in the right hemisphere (RH). In addition, we found greater (non-directional) cortical asymmetries in subjects with larger brains. Asymmetries in subcortical structures included larger LH volumes of thalamus, putamen and globus pallidus and larger RH volumes of the cerebellum and the amygdala. We also found significant correlations between the subcortical structural volumes, particularly of the thalamus and cerebellum, with cortical area. These results help to resolve some of the inconsistencies in previous studies of hemispheric asymmetries in brain anatomy.

  18. Human Frontal–Subcortical Circuit and Asymmetric Belief Updating

    PubMed Central

    Charpentier, Caroline J.; Garrett, Neil; Cohen, Michael X.; Sharot, Tali

    2015-01-01

    How humans integrate information to form beliefs about reality is a question that has engaged scientists for centuries, yet the biological system supporting this process is not well understood. One of the most salient attributes of information is valence. Whether a piece of news is good or bad is critical in determining whether it will alter our beliefs. Here, we reveal a frontal–subcortical circuit in the left hemisphere that is simultaneously associated with enhanced integration of favorable information into beliefs and impaired integration of unfavorable information. Specifically, for favorable information, stronger white matter connectivity within this system, particularly between the left inferior frontal gyrus (IFG) and left subcortical regions (including the amygdala, hippocampus, thalamus, putamen, and pallidum), as well as insular cortex, is associated with greater change in belief. However, for unfavorable information, stronger connectivity within this system, particularly between the left IFG and left pallidum, putamen, and insular cortex, is associated with reduced change in beliefs. These novel results are consistent with models suggesting that partially separable processes govern learning from favorable and unfavorable information. SIGNIFICANCE STATEMENT Beliefs of what may happen in the future are important, because they guide decisions and actions. Here, we illuminate how structural brain connectivity is related to the generation of subjective beliefs. We focus on how the valence of information is related to people's tendency to alter their beliefs. By quantifying the extent to which participants update their beliefs in response to desirable and undesirable information and relating those measures to the strength of white matter connectivity using diffusion tensor imaging, we characterize a left frontal–subcortical system that is associated simultaneously with greater belief updating in response to favorable information and reduced belief

  19. Fractal Dimension Analysis of Subcortical Gray Matter Structures in Schizophrenia

    PubMed Central

    Sehatpour, Pejman; Long, Jun; Gui, Weihua; Qiao, Jianping; Javitt, Daniel C.; Wang, Zhishun

    2016-01-01

    A failure of adaptive inference—misinterpreting available sensory information for appropriate perception and action—is at the heart of clinical manifestations of schizophrenia, implicating key subcortical structures in the brain including the hippocampus. We used high-resolution, three-dimensional (3D) fractal geometry analysis to study subtle and potentially biologically relevant structural alterations (in the geometry of protrusions, gyri and indentations, sulci) in subcortical gray matter (GM) in patients with schizophrenia relative to healthy individuals. In particular, we focus on utilizing Fractal Dimension (FD), a compact shape descriptor that can be computed using inputs with irregular (i.e., not necessarily smooth) surfaces in order to quantify complexity (of geometrical properties and configurations of structures across spatial scales) of subcortical GM in this disorder. Probabilistic (entropy-based) information FD was computed based on the box-counting approach for each of the seven subcortical structures, bilaterally, as well as the brainstem from high-resolution magnetic resonance (MR) images in chronic patients with schizophrenia (n = 19) and age-matched healthy controls (n = 19) (age ranges: patients, 22.7–54.3 and healthy controls, 24.9–51.6 years old). We found a significant reduction of FD in the left hippocampus (median: 2.1460, range: 2.07–2.18 vs. median: 2.1730, range: 2.15–2.23, p<0.001; Cohen’s effect size, U3 = 0.8158 (95% Confidence Intervals, CIs: 0.6316, 1.0)), the right hippocampus (median: 2.1430, range: 2.05–2.19 vs. median: 2.1760, range: 2.12–2.21, p = 0.004; U3 = 0.8421 (CIs: 0.5263, 1)), as well as left thalamus (median: 2.4230, range: 2.40–2.44, p = 0.005; U3 = 0.7895 (CIs: 0.5789, 0.9473)) in schizophrenia patients, relative to healthy individuals. Our findings provide in-vivo quantitative evidence for reduced surface complexity of hippocampus, with reduced FD indicating a less complex, less regular GM

  20. Corticofugal amplification of subcortical responses to single tone stimuli in the mustached bat.

    PubMed

    Zhang, Y; Suga, N

    1997-12-01

    Since 1962, physiological data of corticofugal effects on subcortical auditory neurons have been controversial: inhibitory, excitatory, or both. An inhibitory effect has been much more frequently observed than an excitatory effect. Recent studies performed with an improved experimental design indicate that corticofugal system mediates a highly focused positive feedback to physiologically "matched" subcortical neurons, and widespread lateral inhibition to "unmatched" subcortical neurons, in order to adjust and improve information processing. These results lead to a question: what happens to subcortical auditory responses when the corticofugal system, including matched and unmatched cortical neurons, is functionally eliminated? We temporarily inactivated both matched and unmatched neurons in the primary auditory cortex of the mustached bat with muscimol (an agonist of inhibitory synaptic transmitter) and measured the effect of cortical inactivation on subcortical auditory responses. Cortical inactivation reduced auditory responses in the medial geniculate body and the inferior colliculus. This reduction was larger (60 vs. 34%) and faster (11 vs. 31 min) for thalamic neurons than for collicular neurons. Our data indicate that the corticofugal system amplifies collicular auditory responses by 1.5 times and thalamic responses by 2.5 times on average. The data are consistant with a scheme in which positive feedback from the auditory cortex is modulated by inhibition that may mostly take place in the cortex.

  1. Subcortical correlates of individual differences in aptitude.

    PubMed

    Jung, Rex E; Ryman, Sephira G; Vakhtin, Andrei A; Carrasco, Jessica; Wertz, Chris; Flores, Ranee A

    2014-01-01

    The study of individual differences encompasses broad constructs including intelligence, creativity, and personality. However, substantially less research is devoted to the study of specific aptitudes in spite of their importance to educational, occupational, and avocational success. We sought to determine subcortical brain structural correlates of several broad aptitudes including Math, Vocabulary, Foresight, Paper Folding, and Inductive Reasoning in a large (N = 107), healthy, young (age range  = 16-29) cohort. Subcortical volumes were measured using an automated technique (FreeSurfer) across structures including bilateral caudate, putamen, globus pallidus, thalamus, nucleus accumbens, hippocampus, amygdala, and five equal regions of the corpus callosum. We found that performance on measures of each aptitude was predicted by different subcortical structures: Math--higher right nucleus accumbens volume; Vocabulary--higher left hippocampus volume; Paper Folding--higher right thalamus volume; Foresight--lower right thalamus and higher mid anterior corpus callosum volume; Inductive Reasoning--higher mid anterior corpus callosum volume. Our results support general findings, within the cognitive neurosciences, showing lateralization of structure-function relationships, as well as more specific relationships between individual structures (e.g., left hippocampus) and functions relevant to particular aptitudes (e.g., Vocabulary).

  2. DNA-intercalators Causing Rapid Re-expression of Methylated and Silenced Genes in Cancer Cells

    PubMed Central

    Hossain, M. Zulfiquer; Healey, Megan A.; Lee, Calvin; Poh, Weijie; Yerram, Sashidhar R.; Patel, Kalpesh; Azad, Nilofer S.; Herman, James G.; Kern, Scott E.

    2013-01-01

    Epigenetic inactivation of tumor-suppressor and other regulatory genes plays a critical role in carcinogenesis. Transcriptional silencing is often maintained by DNA methyl transferase (DNMT)-mediated hypermethylation of CpG islands in promoter DNA. Nucleoside analogs including azacytidine and decitabine have been used to inhibit DNMT and re-activate genes, and are clinically used. Their shortcomings include a short half-life and a slow onset of action due to required nucleotide incorporation during DNA replication, which may limit clinical utility. It might be useful to begin to identify lead compounds having novel properties, specifically distinct and fast-acting gene desilencing. We previously identified chemicals augmenting gene expression in multiple reporter systems. We now report that a subset of these compounds that includes quinacrine re-expresses epigenetically silenced genes implicated in carcinogenesis. p16, TFPI2, the cadherins E-cadherin and CDH13, and the secreted frizzle-related proteins (SFRPs) SFRP1 and SFRP5 were desilenced in cancer cell lines. These lead compounds were fast-acting: re-expression occurred by 12-24 hours. Reactivation of silenced genes was accompanied by depletion of DNMT1 at the promoters of activated genes and demethylation of DNA. A model compound, 5175328, induced changes more rapidly than decitabine. These gene desilencing agents belonged to a class of acridine compounds, intercalated into DNA, and inhibited DNMT1 activity in vitro. Although to define the mechanism would be outside the scope of this initial report, this class may re-activate silenced genes in part by intercalating into DNA and subsequently inhibiting full DNMT1 activity. Rapid mechanisms for chemical desilencing of methylated genes therefore exist. PMID:23593653

  3. Large subcortical hemispheric infarctions. Presentation and prognosis.

    PubMed

    Levine, R L; Lagreze, H L; Dobkin, J A; Turski, P A

    1988-10-01

    A specific form of large subcortical hemispheric infarction on computed tomography was identified in 24 of 2198 (1%) stroke registry patients. Combined with 13 cases from earlier literature reports, a characteristic neurologic picture developed. Severe face plus arm plus leg weakness at onset (76%), corticallike features of aphasia and/or contralateral neglect (68%), and premonitory transient ischemic attacks (24%) were frequent. Twenty-two patients (59%) had large vessel arterial occlusive disease. Eight patients (22%) had primary embolic occlusion in the middle cerebral artery territory. During an average follow-up of 16 months, five patients (14%) suffered recurrent stroke or death. The clinical presentation and prognostic features of this distinct stroke subtype are described.

  4. Cortical-Subcortical Interactions in Depression: From Animal Models to Human Psychopathology

    PubMed Central

    Heller, Aaron S.

    2016-01-01

    Depression is a debilitating disorder causing significant societal and personal suffering. Improvements in identification of major depressive disorder (MDD) and its treatment are essential to reduce its toll. Recent developments in rodent models of MDD and neuroimaging of humans suffering from the disorder provide avenues through which gains can be made towards reducing its burden. In this review, new findings, integrating across rodent models and human imaging are highlighted that have yielded new insights towards a basic understanding of the disorder. In particular, this review focuses on cortical-subcortical interactions underlying the pathophysiology of MDD. In particular, evidence is accruing that dysfunction in prefrontal-subcortical circuits including the amygdala, ventral striatum (VS), hippocampus and dorsal raphe nucleus (DRN) are associated with MDD status. PMID:27013988

  5. Subcortical and cerebellar volumetric deficits in paediatric sickle cell anaemia.

    PubMed

    Kawadler, Jamie M; Clayden, Jonathan D; Kirkham, Fenella J; Cox, Timothy C; Saunders, Dawn E; Clark, Chris A

    2013-11-01

    Sickle cell anaemia (SCA) is associated with silent cerebral infarction (SCI), affecting white and cortical grey matter, but there are few data on subcortical volumes. We analysed retrospective magnetic resonance imaging (MRI) data in 26 SCA patients and 20 controls, comparing mean subcortical volumes between three groups: controls, SCA with SCI (n = 13) and SCA without visible abnormality (n = 13). Specific volumetric differences were found in the hippocampus, amygdala, pallidum, caudate, putamen, thalamus, and cerebellum. This is the first study to demonstrate subcortical volume change in SCA, with the most severe volumetric deficits occurring in children with SCI seen on MRI.

  6. Viscoelasticity of subcortical gray matter structures.

    PubMed

    Johnson, Curtis L; Schwarb, Hillary; D J McGarry, Matthew; Anderson, Aaron T; Huesmann, Graham R; Sutton, Bradley P; Cohen, Neal J

    2016-12-01

    Viscoelastic mechanical properties of the brain assessed with magnetic resonance elastography (MRE) are sensitive measures of microstructural tissue health in neurodegenerative conditions. Recent efforts have targeted measurements localized to specific neuroanatomical regions differentially affected in disease. In this work, we present a method for measuring the viscoelasticity in subcortical gray matter (SGM) structures, including the amygdala, hippocampus, caudate, putamen, pallidum, and thalamus. The method is based on incorporating high spatial resolution MRE imaging (1.6 mm isotropic voxels) with a mechanical inversion scheme designed to improve local measures in pre-defined regions (soft prior regularization [SPR]). We find that in 21 healthy, young volunteers SGM structures differ from each other in viscoelasticity, quantified as the shear stiffness and damping ratio, but also differ from the global viscoelasticity of the cerebrum. Through repeated examinations on a single volunteer, we estimate the uncertainty to be between 3 and 7% for each SGM measure. Furthermore, we demonstrate that the use of specific methodological considerations-higher spatial resolution and SPR-both decrease uncertainty and increase sensitivity of the SGM measures. The proposed method allows for reliable MRE measures of SGM viscoelasticity for future studies of neurodegenerative conditions. Hum Brain Mapp 37:4221-4233, 2016. © 2016 Wiley Periodicals, Inc.

  7. Processing of frequency and location in human subcortical auditory structures

    PubMed Central

    Moerel, Michelle; De Martino, Federico; Uğurbil, Kâmil; Yacoub, Essa; Formisano, Elia

    2015-01-01

    To date it remains largely unknown how fundamental aspects of natural sounds, such as their spectral content and location in space, are processed in human subcortical structures. Here we exploited the high sensitivity and specificity of high field fMRI (7 Tesla) to examine the human inferior colliculus (IC) and medial geniculate body (MGB). Subcortical responses to natural sounds were well explained by an encoding model of sound processing that represented frequency and location jointly. Frequency tuning was organized in one tonotopic gradient in the IC, whereas two tonotopic maps characterized the MGB reflecting two MGB subdivisions. In contrast, no topographic pattern of preferred location was detected, beyond an overall preference for peripheral (as opposed to central) and contralateral locations. Our findings suggest the functional organization of frequency and location processing in human subcortical auditory structures, and pave the way for studying the subcortical to cortical interaction required to create coherent auditory percepts. PMID:26597173

  8. Re-expression of Selected Epigenetically Silenced Candidate Tumor Suppressor Genes in Cervical Cancer by TET2-directed Demethylation.

    PubMed

    Huisman, Christian; van der Wijst, Monique G P; Schokker, Matthijs; Blancafort, Pilar; Terpstra, Martijn M; Kok, Klaas; van der Zee, Ate G J; Schuuring, Ed; Wisman, G Bea A; Rots, Marianne G

    2016-03-01

    DNA hypermethylation is extensively explored as therapeutic target for gene expression modulation in cancer. Here, we re-activated hypermethylated candidate tumor suppressor genes (TSGs) (C13ORF18, CCNA1, TFPI2, and Maspin) by TET2-induced demethylation in cervical cancer cell lines. To redirect TET2 to hypermethylated TSGs, we engineered zinc finger proteins (ZFPs), which were first fused to the transcriptional activator VP64 to validate effective gene re-expression and confirm TSG function. ChIP-Seq not only revealed enriched binding of ZFPs to their intended sequence, but also considerable off-target binding, especially at promoter regions. Nevertheless, results obtained by targeted re-expression using ZFP-VP64 constructs were in line with cDNA overexpression; both revealed strong growth inhibition for C13ORF18 and TFPI2, but not for CCNA1 and Maspin. To explore effectivity of locus-targeted demethylation, ZFP-TET2 fusions were constructed which efficiently demethylated genes with subsequent gene re-activation. Moreover, targeting TET2 to TFPI2 and C13ORF18, but not CCNA1, significantly decreased cell growth, viability, and colony formation in cervical cancer cells compared to a catalytically inactive mutant of TET2. These data underline that effective re-activation of hypermethylated genes can be achieved through targeted DNA demethylation by TET2, which can assist in realizing sustained re-expression of genes of interest.

  9. Childhood adversity impacts on brain subcortical structures relevant to depression.

    PubMed

    Frodl, Thomas; Janowitz, Deborah; Schmaal, Lianne; Tozzi, Leonardo; Dobrowolny, Henrik; Stein, Dan J; Veltman, Dick J; Wittfeld, Katharina; van Erp, Theo G M; Jahanshad, Neda; Block, Andrea; Hegenscheid, Katrin; Völzke, Henry; Lagopoulos, Jim; Hatton, Sean N; Hickie, Ian B; Frey, Eva Maria; Carballedo, Angela; Brooks, Samantha J; Vuletic, Daniella; Uhlmann, Anne; Veer, Ilya M; Walter, Henrik; Schnell, Knut; Grotegerd, Dominik; Arolt, Volker; Kugel, Harald; Schramm, Elisabeth; Konrad, Carsten; Zurowski, Bartosz; Baune, Bernhard T; van der Wee, Nic J A; van Tol, Marie-Jose; Penninx, Brenda W J H; Thompson, Paul M; Hibar, Derrek P; Dannlowski, Udo; Grabe, Hans J

    2017-03-01

    Childhood adversity plays an important role for development of major depressive disorder (MDD). There are differences in subcortical brain structures between patients with MDD and healthy controls, but the specific impact of childhood adversity on such structures in MDD remains unclear. Thus, aim of the present study was to investigate whether childhood adversity is associated with subcortical volumes and how it interacts with a diagnosis of MDD and sex. Within the ENIGMA-MDD network, nine university partner sites, which assessed childhood adversity and magnetic resonance imaging in patients with MDD and controls, took part in the current joint mega-analysis. In this largest effort world-wide to identify subcortical brain structure differences related to childhood adversity, 3036 participants were analyzed for subcortical brain volumes using FreeSurfer. A significant interaction was evident between childhood adversity, MDD diagnosis, sex, and region. Increased exposure to childhood adversity was associated with smaller caudate volumes in females independent of MDD. All subcategories of childhood adversity were negatively associated with caudate volumes in females - in particular emotional neglect and physical neglect (independently from age, ICV, imaging site and MDD diagnosis). There was no interaction effect between childhood adversity and MDD diagnosis on subcortical brain volumes. Childhood adversity is one of the contributors to brain structural abnormalities. It is associated with subcortical brain abnormalities that are relevant to psychiatric disorders such as depression.

  10. Subcortical shape and volume abnormalities in an elderly HIV+ cohort

    NASA Astrophysics Data System (ADS)

    Wade, Benjamin S. C.; Valcour, Victor; Busovaca, Edgar; Esmaeili-Firidouni, Pardis; Joshi, Shantanu H.; Wang, Yalin; Thompson, Paul M.

    2015-03-01

    Over 50% of HIV+ individuals show significant impairment in psychomotor functioning, processing speed, working memory and attention [1, 2]. Patients receiving combination antiretroviral therapy may still have subcortical atrophy, but the profile of HIV-associated brain changes is poorly understood. With parametric surface-based shape analyses, we mapped the 3D profile of subcortical morphometry in 63 elderly HIV+ subjects (4 female; age=65.35 ± 2.21) and 31 uninfected elderly controls (2 female; age=64.68 ± 4.57) scanned with MRI as part of a San Francisco Bay Area study of elderly people with HIV. We also investigated whether morphometry was associated with nadir CD4+ (T-cell) counts, viral load and illness duration among HIV+ participants. FreeSurfer was used to segment the thalamus, caudate, putamen, pallidum, hippocampus, amygdala, accumbens, brainstem, callosum and ventricles from brain MRI scans. To study subcortical shape, we analyzed: (1) the Jacobian determinant (JD) indexed over structures' surface coordinates and (2) radial distances (RD) of structure surfaces from a medial curve. A JD less than 1 reflects regional tissue atrophy and greater than 1 reflects expansion. The volumes of several subcortical regions were found to be associated with HIV status. No regional volumes showed detectable associations with CD4 counts, viral load or illness duration. The shapes of numerous subcortical regions were significantly linked to HIV status, detectability of viral RNA and illness duration. Our results show subcortical brain differences in HIV+ subjects in both shape and volumetric domains.

  11. Neural mechanisms of emotion regulation: Evidence for two independent prefrontal-subcortical pathways

    PubMed Central

    Wager, Tor D.; Davidson, Matthew L.; Hughes, Brent L.; Lindquist, Martin A.; Ochsner, Kevin N.

    2008-01-01

    Although prefrontal cortex has been implicated in the cognitive regulation of emotion, the cortical-subcortical interactions that mediate this ability remain poorly understood. To address this issue, we identified a right ventrolateral prefrontal region (vlPFC) whose activity correlated with reduced negative emotional experience during cognitive reappraisal of aversive images. We then applied a novel pathway-mapping analysis on subcortical regions to locate mediators of the association between vlPFC activity and reappraisal success (i.e. reductions in reported emotion). Results identified two separable pathways that together explained ~50% of the reported variance in self-reported emotion: 1) a path through nucleus accumbens that predicted greater reappraisal success, and 2) a path through ventral amygdala that predicted reduced reappraisal success (i.e., more negative emotion). These results provide direct evidence that vlPFC is involved in both the generation and regulation of emotion through different subcortical pathways, suggesting a general role for this region in appraisal processes. PMID:18817740

  12. Subcortical volumetric abnormalities in bipolar disorder

    PubMed Central

    Hibar, D P; Westlye, L T; van Erp, T G M; Rasmussen, J; Leonardo, C D; Faskowitz, J; Haukvik, U K; Hartberg, C B; Doan, N T; Agartz, I; Dale, A M; Gruber, O; Krämer, B; Trost, S; Liberg, B; Abé, C; Ekman, C J; Ingvar, M; Landén, M; Fears, S C; Freimer, N B; Bearden, C E; Sprooten, E; Glahn, D C; Pearlson, G D; Emsell, L; Kenney, J; Scanlon, C; McDonald, C; Cannon, D M; Almeida, J; Versace, A; Caseras, X; Lawrence, N S; Phillips, M L; Dima, D; Delvecchio, G; Frangou, S; Satterthwaite, T D; Wolf, D; Houenou, J; Henry, C; Malt, U F; Bøen, E; Elvsåshagen, T; Young, A H; Lloyd, A J; Goodwin, G M; Mackay, C E; Bourne, C; Bilderbeck, A; Abramovic, L; Boks, M P; van Haren, N E M; Ophoff, R A; Kahn, R S; Bauer, M; Pfennig, A; Alda, M; Hajek, T; Mwangi, B; Soares, J C; Nickson, T; Dimitrova, R; Sussmann, J E; Hagenaars, S; Whalley, H C; McIntosh, A M; Thompson, P M; Andreassen, O A

    2016-01-01

    Considerable uncertainty exists about the defining brain changes associated with bipolar disorder (BD). Understanding and quantifying the sources of uncertainty can help generate novel clinical hypotheses about etiology and assist in the development of biomarkers for indexing disease progression and prognosis. Here we were interested in quantifying case–control differences in intracranial volume (ICV) and each of eight subcortical brain measures: nucleus accumbens, amygdala, caudate, hippocampus, globus pallidus, putamen, thalamus, lateral ventricles. In a large study of 1710 BD patients and 2594 healthy controls, we found consistent volumetric reductions in BD patients for mean hippocampus (Cohen's d=−0.232; P=3.50 × 10−7) and thalamus (d=−0.148; P=4.27 × 10−3) and enlarged lateral ventricles (d=−0.260; P=3.93 × 10−5) in patients. No significant effect of age at illness onset was detected. Stratifying patients based on clinical subtype (BD type I or type II) revealed that BDI patients had significantly larger lateral ventricles and smaller hippocampus and amygdala than controls. However, when comparing BDI and BDII patients directly, we did not detect any significant differences in brain volume. This likely represents similar etiology between BD subtype classifications. Exploratory analyses revealed significantly larger thalamic volumes in patients taking lithium compared with patients not taking lithium. We detected no significant differences between BDII patients and controls in the largest such comparison to date. Findings in this study should be interpreted with caution and with careful consideration of the limitations inherent to meta-analyzed neuroimaging comparisons. PMID:26857596

  13. Cortical dynamics and subcortical signatures of motor-language coupling in Parkinson’s disease

    PubMed Central

    Melloni, Margherita; Sedeño, Lucas; Hesse, Eugenia; García-Cordero, Indira; Mikulan, Ezequiel; Plastino, Angelo; Marcotti, Aida; López, José David; Bustamante, Catalina; Lopera, Francisco; Pineda, David; García, Adolfo M.; Manes, Facundo; Trujillo, Natalia; Ibáñez, Agustín

    2015-01-01

    Impairments of action language have been documented in early stage Parkinson’s disease (EPD). The action-sentence compatibility effect (ACE) paradigm has revealed that EPD involves deficits to integrate action-verb processing and ongoing motor actions. Recent studies suggest that an abolished ACE in EPD reflects a cortico-subcortical disruption, and recent neurocognitive models highlight the role of the basal ganglia (BG) in motor-language coupling. Building on such breakthroughs, we report the first exploration of convergent cortical and subcortical signatures of ACE in EPD patients and matched controls. Specifically, we combined cortical recordings of the motor potential, functional connectivity measures, and structural analysis of the BG through voxel-based morphometry. Relative to controls, EPD patients exhibited an impaired ACE, a reduced motor potential, and aberrant frontotemporal connectivity. Furthermore, motor potential abnormalities during the ACE task were predicted by overall BG volume and atrophy. These results corroborate that motor-language coupling is mainly subserved by a cortico-subcortical network including the BG as a key hub. They also evince that action-verb processing may constitute a neurocognitive marker of EPD. Our findings suggest that research on the relationship between language and motor domains is crucial to develop models of motor cognition as well as diagnostic and intervention strategies. PMID:26152329

  14. Treatment of seizures in subcortical laminar heterotopia with corpus callosotomy and lamotrigine.

    PubMed

    Vossler, D G; Lee, J K; Ko, T S

    1999-05-01

    Focal and generalized cortical dysgeneses are sometimes seen on the magnetic resonance images (MRI) of patients with epilepsy. Subcortical laminar heterotopia are bilateral collections of gray matter in the centrum semiovale that resemble a band or "double cortex" on MRI. We studied one male and two female patients with subcortical laminar heterotopia who had moderate to severe developmental delay, early-onset epilepsy, and medically refractory seizures. Atonic, atypical absence, tonic, myoclonic, complex partial, and generalized tonic-clonic seizures were recorded. Interictal and ictal electroencephalographic patterns were generalized and, less commonly, multifocal. Two years after corpus callosotomy, one patient was free of generalized tonic-clonic and atonic seizures, but the other patient who had undergone callosotomy had no significant reduction in seizure frequency. With lamotrigine treatment, the patient who had not had surgery had complete cessation of monthly episodes of status epilepticus and a dramatic reduction of generalized tonic-clonic seizures, and the other patient who received lamotrigine had a 50% reduction of her atonic seizures. In patients with subcortical laminar heterotopia, atonic and generalized tonic-clonic seizures can be substantially reduced or eliminated by corpus callosotomy or treatment with lamotrigine.

  15. Megalencephalic leukoencephalopathy with subcortical cysts protein-1 regulates epidermal growth factor receptor signaling in astrocytes.

    PubMed

    Lanciotti, Angela; Brignone, Maria Stefania; Visentin, Sergio; De Nuccio, Chiara; Catacuzzeno, Luigi; Mallozzi, Cinzia; Petrini, Stefania; Caramia, Martino; Veroni, Caterina; Minnone, Gaetana; Bernardo, Antonietta; Franciolini, Fabio; Pessia, Mauro; Bertini, Enrico; Petrucci, Tamara Corinna; Ambrosini, Elena

    2016-04-15

    Mutations in the MLC1 gene, which encodes a protein expressed in brain astrocytes, are the leading cause of MLC, a rare leukodystrophy characterized by macrocephaly, brain edema, subcortical cysts, myelin and astrocyte vacuolation. Although recent studies indicate that MLC1 protein is implicated in the regulation of cell volume changes, the exact role of MLC1 in brain physiology and in the pathogenesis of MLC disease remains to be clarified. In preliminary experiments, we observed that MLC1 was poorly expressed in highly proliferating astrocytoma cells when compared with primary astrocytes, and that modulation of MLC1 expression influenced astrocyte growth. Because volume changes are key events in cell proliferation and during brain development MLC1 expression is inversely correlated to astrocyte progenitor proliferation levels, we investigated the possible role for MLC1 in the control of astrocyte proliferation. We found that overexpression of wild type but not mutant MLC1 in human astrocytoma cells hampered cell growth by favoring epidermal growth factor receptor (EGFR) degradation and by inhibiting EGF-induced Ca(+) entry, ERK1/2 and PLCγ1 activation, and calcium-activated KCa3.1 potassium channel function, all molecular pathways involved in astrocyte proliferation stimulation. Interestingly, MLC1 did not influence AKT, an EGFR-stimulated kinase involved in cell survival. Moreover, EGFR expression was higher in macrophages derived from MLC patients than from healthy individuals. Since reactive astrocytes proliferate and re-express EGFR in response to different pathological stimuli, the present findings provide new information on MLC pathogenesis and unravel an important role for MLC1 in other brain pathological conditions where astrocyte activation occurs.

  16. Physical fitness and shapes of subcortical brain structures in children.

    PubMed

    Ortega, Francisco B; Campos, Daniel; Cadenas-Sanchez, Cristina; Altmäe, Signe; Martínez-Zaldívar, Cristina; Martín-Matillas, Miguel; Catena, Andrés; Campoy, Cristina

    2017-03-27

    A few studies have recently reported that higher cardiorespiratory fitness is associated with higher volumes of subcortical brain structures in children. It is, however, unknown how different fitness measures relate to shapes of subcortical brain nuclei. We aimed to examine the association of the main health-related physical fitness components with shapes of subcortical brain structures in a sample of forty-four Spanish children aged 9·7 (sd 0·2) years from the NUtraceuticals for a HEALthier life project. Cardiorespiratory fitness, muscular strength and speed agility were assessed using valid and reliable tests (ALPHA-fitness test battery). Shape of the subcortical brain structures was assessed by MRI, and its relationship with fitness was examined after controlling for a set of potential confounders using a partial correlation permutation approach. Our results showed that all physical fitness components studied were significantly related to the shapes of subcortical brain nuclei. These associations were both positive and negative, indicating that a higher level of fitness in childhood is related to both expansions and contractions in certain regions of the accumbens, amygdala, caudate, hippocampus, pallidum, putamen and thalamus. Cardiorespiratory fitness was mainly associated with expansions, whereas handgrip was mostly associated with contractions in the structures studied. Future randomised-controlled trials will confirm or contrast our findings, demonstrating whether changes in fitness modify the shapes of brain structures and the extent to which those changes influence cognitive function.

  17. Cortical gray and subcortical white matter associations in Parkinson's disease.

    PubMed

    Sterling, Nicholas W; Du, Guangwei; Lewis, Mechelle M; Swavely, Steven; Kong, Lan; Styner, Martin; Huang, Xuemei

    2017-01-01

    Cortical atrophy has been documented in both Parkinson's disease (PD) and healthy aging, but its relationship to changes in subcortical white matter is unknown. This was investigated by obtaining T1- and diffusion-weighted images from 76 PD and 70 controls at baseline and 18 and 36 months, from which cortical volumes and underlying subcortical white matter axial diffusivity (AD), radial diffusivity (RD), and fractional anisotropy (FA) were determined. Twelve of 69 cortical subregions had significant group differences, and for these, underlying subcortical white matter was explored. At baseline, higher cortical volumes were significantly correlated with lower underlying subcortical white matter AD, RD, and higher FA (ps ≤ 0.017) in PD. Longitudinally, higher rates of cortical atrophy in PD were associated with increased rates of change in AD RD, and FA values (ps ≤ 0.0013) in 2 subregions explored. The significant gray-white matter associations were not found in controls. Thus, unlike healthy aging, cortical atrophy and subcortical white matter changes may not be independent events in PD.

  18. Subcortical mapping of calculation processing in the right parietal lobe.

    PubMed

    Della Puppa, Alessandro; De Pellegrin, Serena; Lazzarini, Anna; Gioffrè, Giorgio; Rustemi, Oriela; Cagnin, Annachiara; Scienza, Renato; Semenza, Carlo

    2015-05-01

    Preservation of calculation processing in brain surgery is crucial for patients' quality of life. Over the last decade, surgical electrostimulation was used to identify and preserve the cortical areas involved in such processing. Conversely, subcortical connectivity among different areas implicated in this function remains unclear, and the role of surgery in this domain has not been explored so far. The authors present the first 2 cases in which the subcortical functional sites involved in calculation were identified during right parietal lobe surgery. Two patients affected by a glioma located in the right parietal lobe underwent surgery with the aid of MRI neuronavigation. No calculation deficits were detected during preoperative assessment. Cortical and subcortical mapping were performed using a bipolar stimulator. The current intensity was determined by progressively increasing the amplitude by 0.5-mA increments (from a baseline of 1 mA) until a sensorimotor response was elicited. Then, addition and multiplication calculation tasks were administered. Corticectomy was performed according to both the MRI neuronavigation data and the functional findings obtained through cortical mapping. Direct subcortical electrostimulation was repeatedly performed during tumor resection. Subcortical functional sites for multiplication and addition were detected in both patients. Electrostimulation interfered with calculation processing during cortical mapping as well. Functional sites were spared during tumor removal. The postoperative course was uneventful, and calculation processing was preserved. Postoperative MRI showed complete resection of the tumor. The present preliminary study shows for the first time how functional mapping can be a promising method to intraoperatively identify the subcortical functional sites involved in calculation processing. This report therefore supports direct electrical stimulation as a promising tool to improve the current knowledge on

  19. Abnormal asymmetries in subcortical brain volume in schizophrenia

    PubMed Central

    Okada, N; Fukunaga, M; Yamashita, F; Koshiyama, D; Yamamori, H; Ohi, K; Yasuda, Y; Fujimoto, M; Watanabe, Y; Yahata, N; Nemoto, K; Hibar, D P; van Erp, T G M; Fujino, H; Isobe, M; Isomura, S; Natsubori, T; Narita, H; Hashimoto, N; Miyata, J; Koike, S; Takahashi, T; Yamasue, H; Matsuo, K; Onitsuka, T; Iidaka, T; Kawasaki, Y; Yoshimura, R; Watanabe, Y; Suzuki, M; Turner, J A; Takeda, M; Thompson, P M; Ozaki, N; Kasai, K; Hashimoto, R

    2016-01-01

    Subcortical structures, which include the basal ganglia and parts of the limbic system, have key roles in learning, motor control and emotion, but also contribute to higher-order executive functions. Prior studies have reported volumetric alterations in subcortical regions in schizophrenia. Reported results have sometimes been heterogeneous, and few large-scale investigations have been conducted. Moreover, few large-scale studies have assessed asymmetries of subcortical volumes in schizophrenia. Here, as a work completely independent of a study performed by the ENIGMA consortium, we conducted a large-scale multisite study of subcortical volumetric differences between patients with schizophrenia and controls. We also explored the laterality of subcortical regions to identify characteristic similarities and differences between them. T1-weighted images from 1680 healthy individuals and 884 patients with schizophrenia, obtained with 15 imaging protocols at 11 sites, were processed with FreeSurfer. Group differences were calculated for each protocol and meta-analyzed. Compared with controls, patients with schizophrenia demonstrated smaller bilateral hippocampus, amygdala, thalamus and accumbens volumes as well as intracranial volume, but larger bilateral caudate, putamen, pallidum and lateral ventricle volumes. We replicated the rank order of effect sizes for subcortical volumetric changes in schizophrenia reported by the ENIGMA consortium. Further, we revealed leftward asymmetry for thalamus, lateral ventricle, caudate and putamen volumes, and rightward asymmetry for amygdala and hippocampal volumes in both controls and patients with schizophrenia. Also, we demonstrated a schizophrenia-specific leftward asymmetry for pallidum volume. These findings suggest the possibility of aberrant laterality in neural pathways and connectivity patterns related to the pallidum in schizophrenia. PMID:26782053

  20. Oligoamine analogues in combination with 2-difluoromethylornithine synergistically induce re-expression of aberrantly silenced tumour-suppressor genes.

    PubMed

    Wu, Yu; Steinbergs, Nora; Murray-Stewart, Tracy; Marton, Laurence J; Casero, Robert A

    2012-03-15

    Epigenetic gene silencing is an important mechanism in the initiation and progression of cancer. Abnormal DNA CpG island hypermethylation and histone modifications are involved in aberrant silencing of tumour-suppressor genes. LSD1 (lysine-specific demethylase 1) was the first enzyme identified to specifically demethylate H3K4 (Lys(4) of histone H3). Methylated H3K4 is an important mark associated with transcriptional activation. The flavin adenine dinucleotide-binding amine oxidase domain of LSD1 is homologous with two polyamine oxidases, SMO (spermine oxidase) and APAO (N(1)-acetylpolyamine oxidase). We have demonstrated previously that long-chain polyamine analogues, the oligoamines, are inhibitors of LSD1. In the present paper we report the synergistic effects of specific oligoamines in combination with DFMO (2-difluoromethylornithine), an inhibitor of ornithine decarboxylase, in human colorectal cancer cells. DFMO treatment depletes natural polyamines and increases the uptake of exogenous polyamines. The combination of oligoamines and DFMO results in a synergistic re-expression of aberrantly silenced tumour-suppressor genes, including SFRP2 (secreted frizzled-related protein 2), which encodes a Wnt signalling pathway antagonist and plays an anti-tumorigenic role in colorectal cancer. The treatment-induced re-expression of SFRP2 is associated with increased H3K4me2 (di-methyl H3K4) in the gene promoter. The combination of LSD1-inhibiting oligoamines and DFMO represents a novel approach to epigenetic therapy of cancer.

  1. Oligoamine analogues in combination with 2-difluoromethylornithine synergistically induce re-expression of aberrantly silenced tumour-suppressor genes

    PubMed Central

    Wu, Yu; Steinbergs, Nora; Murray-Stewart, Tracy; Marton, Laurence J.; Casero, Robert A.

    2011-01-01

    Epigenetic gene silencing is an important mechanism in the initiation and progression of cancer. Abnormal DNA CpG island hypermethylation and histone modifications are involved in aberrant silencing of tumour-suppressor genes. LSD1 (lysine-specific demethylase 1) was the first enzyme identified to specifically demethylate H3K4 (Lys4 of histone H3). Methylated H3K4 is an important mark associated with transcriptional activation. The flavin adenine dinucleotide-binding amine oxidase domain of LSD1 is homologous with two polyamine oxidases, SMO (spermine oxidase) and APAO (N1-acetylpolyamine oxidase). We have demonstrated previously that long-chain polyamine analogues, the oligoamines, are inhibitors of LSD1. In the present paper we report the synergistic effects of specific oligoamines in combination with DFMO (2-difluoromethylornithine), an inhibitor of ornithine decarboxylase, in human colorectal cancer cells. DFMO treatment depletes natural polyamines and increases the uptake of exogenous polyamines. The combination of oligoamines and DFMO results in a synergistic re-expression of aberrantly silenced tumour-suppressor genes, including SFRP2 (secreted frizzled-related protein 2), which encodes a Wnt signalling pathway antagonist and plays an anti-tumorigenic role in colorectal cancer. The treatment-induced re-expression of SFRP2 is associated with increased H3K4me2 (di-methyl H3K4) in the gene promoter. The combination of LSD1-inhibiting oligoamines and DFMO represents a novel approach to epigenetic therapy of cancer. PMID:22132744

  2. Impact of subcortical white matter lesions on dopamine transporter SPECT.

    PubMed

    Funke, Elisabeth; Kupsch, Andreas; Buchert, Ralph; Brenner, Winfried; Plotkin, Michail

    2013-07-01

    Subcortical arteriosclerotic encephalopathy (SAE) can affect the nigrostriatal system and presumably cause vascular parkinsonism (VP). However, in patients with SAE, the differentiation of VP from idiopathic Parkinson's disease (IPS) is challenging. The aim of the present study was to examine the striatal dopamine transporter (DAT) density in patients with parkinsonism and SAE. Fifteen consecutive patients with parkinsonian symptoms displayed SAE, as detected by magnetic resonance imaging (MRI). Fifteen retrospectively chosen, matched patients with diagnosis of IPS without any abnormalities in MRI served as a reference group. DAT SPECT was performed using the tracer ¹²³I-FP-CIT. Scans were acquired on a triple-head SPECT system (Multispect 3, Siemens) and analysed using the investigator-independent BRASS™ software (HERMES). In the SAE group, a DAT deficit was observed in 9/15 patients. In contrast, all patients from the IPS group showed a reduced DAT binding (p = 0.008). The specific binding ratios (BR) of putamen contralateral to the side of the more affected limb versus occipital lobe were in trend higher in patients with SAE versus patients in the IPS-group (p = 0.053). Indices for putaminal asymmetry (p = 0.036) and asymmetry caudate-to-putamen (p = 0.026) as well as the ratio caudate-to-putamen (p = 0.048) were significantly higher in IPS patients having no SAE. DAT deficit was less pronounced in patients with SAE and parkinsonism than in patients with IPS without any abnormalities in the MRI. A potential role of DAT SPECT in the differential diagnosis of VP and IPS requires more assessments within prospective studies.

  3. Neuropsychological Profile of Children with Subcortical Band Heterotopia

    ERIC Educational Resources Information Center

    Spencer-Smith, Megan; Leventer, Richard; Jacobs, Rani; De Luca, Cinzia; Anderson, Vicki

    2009-01-01

    Aim: Subcortical band heterotopia (SBH) or "double cortex" is a malformation of cortical development resulting from impaired neuronal migration. So far, research has focused on the neurological, neuroimaging, and genetic correlates of SBH. More recently, clinical reports and small sample studies have documented neuropsychological dysfunction in…

  4. Phonemic Characteristics of Apraxia of Speech Resulting from Subcortical Hemorrhage

    ERIC Educational Resources Information Center

    Peach, Richard K.; Tonkovich, John D.

    2004-01-01

    Reports describing subcortical apraxia of speech (AOS) have received little consideration in the development of recent speech processing models because the speech characteristics of patients with this diagnosis have not been described precisely. We describe a case of AOS with aphasia secondary to basal ganglia hemorrhage. Speech-language symptoms…

  5. Statistical shape analysis of subcortical structures using spectral matching.

    PubMed

    Shakeri, Mahsa; Lombaert, Herve; Datta, Alexandre N; Oser, Nadine; Létourneau-Guillon, Laurent; Lapointe, Laurence Vincent; Martin, Florence; Malfait, Domitille; Tucholka, Alan; Lippé, Sarah; Kadoury, Samuel

    2016-09-01

    Studying morphological changes of subcortical structures often predicate neurodevelopmental and neurodegenerative diseases, such as Alzheimer's disease and schizophrenia. Hence, methods for quantifying morphological variations in the brain anatomy, including groupwise shape analyses, are becoming increasingly important for studying neurological disorders. In this paper, a novel groupwise shape analysis approach is proposed to detect regional morphological alterations in subcortical structures between two study groups, e.g., healthy and pathological subjects. The proposed scheme extracts smoothed triangulated surface meshes from segmented binary maps, and establishes reliable point-to-point correspondences among the population of surfaces using a spectral matching method. Mean curvature features are incorporated in the matching process, in order to increase the accuracy of the established surface correspondence. The mean shapes are created as the geometric mean of all surfaces in each group, and a distance map between these shapes is used to characterize the morphological changes between the two study groups. The resulting distance map is further analyzed to check for statistically significant differences between two populations. The performance of the proposed framework is evaluated on two separate subcortical structures (hippocampus and putamen). Furthermore, the proposed methodology is validated in a clinical application for detecting abnormal subcortical shape variations in Alzheimer's disease. Experimental results show that the proposed method is comparable to state-of-the-art algorithms, has less computational cost, and is more sensitive to small morphological variations in patients with neuropathologies.

  6. Aphasia owing to subcortical brain infarcts in childhood.

    PubMed

    Gout, Ariel; Seibel, Nathalie; Rouvière, Constance; Husson, Béatrice; Hermans, Brigitte; Laporte, Nicole; Kadhim, Hazim; Grin, Cécile; Landrieu, Pierre; Sébire, Guillaume

    2005-12-01

    The aim of this study was to further define the clinical features of subcortical aphasia in children with deep brain infarcts and to define the sequelae associated with childhood strokes. We retrospectively studied nine children with left subcortical brain infarcts who presented with acquired language disorder and underwent language investigations based on standardized tests. Stroke in these patients involved the left internal capsule, lenticular or thalamic nuclei, or a combination of these. Early aphasic manifestations following the deep cerebral infarcts affected language expression. These included mutism, nonfluent speech, word finding difficulties, and phonemic and semantic paraphasia. Speech comprehension was generally more preserved. All patients subsequently improved, although variably; sequelae such as dysfluency, word finding difficulties, and written language learning impairment could be detected through standardized tests in six of them (all younger than 6 years at the time of the infarct). Two of the three remaining patients (both older than 6 years at the time of the infarct) had a full recovery. Our study confirms the concept of childhood subcortical aphasia, depicts the linguistic profile in these patients, and sustains the indication of systematic formal language assessment during the follow-up of all children with subcortical infarct involving the dominant hemisphere.

  7. Top-Down-Mediated Facilitation in the Visual Cortex Is Gated by Subcortical Neuromodulation

    PubMed Central

    Pafundo, Diego E.; Nicholas, Mark A.; Zhang, Ruilin

    2016-01-01

    Response properties in primary sensory cortices are highly dependent on behavioral state. For example, the nucleus basalis of the forebrain plays a critical role in enhancing response properties of excitatory neurons in primary visual cortex (V1) during active exploration and learning. Given the strong reciprocal connections between hierarchically arranged cortical regions, how are increases in sensory response gain constrained to prevent runaway excitation? To explore this, we used in vivo two-photon guided cell-attached recording in conjunction with spatially restricted optogenetic photo-inhibition of higher-order visual cortex in mice. We found that the principle feedback projection to V1 originating from the lateral medial area (LM) facilitated visual responses in layer 2/3 excitatory neurons by ∼20%. This facilitation was reduced by half during basal forebrain activation due to differential response properties between LM and V1. Our results demonstrate that basal-forebrain-mediated increases in response gain are localized to V1 and are not propagated to LM and establish that subcortical modulation of visual cortex is regionally distinct. SIGNIFICANCE STATEMENT Reciprocal connectivity among brain regions is a prominent feature of all sensory cortices. In primary visual cortex (V1), top-down signals from association areas aid in context-dependent perception of visual scenes by altering the response properties of individual neurons. Sensory-evoked responses in V1 are also highly dependent on subcortical neuromodulation pathways that regulate brain state. Here, with cell-type-specific resolution, we addressed how corticocortical and subcortical pathways interact to regulate responsiveness of V1. Our results provide insight into the rules and conditions governing activity propagation in reciprocally connected networks. PMID:26961946

  8. Subcortical Shape Changes, Hippocampal Atrophy and Cortical Thinning in Future Alzheimer's Disease Patients.

    PubMed

    Kälin, Andrea M; Park, Min T M; Chakravarty, M Mallar; Lerch, Jason P; Michels, Lars; Schroeder, Clemens; Broicher, Sarah D; Kollias, Spyros; Nitsch, Roger M; Gietl, Anton F; Unschuld, Paul G; Hock, Christoph; Leh, Sandra E

    2017-01-01

    Efficacy of future treatments depends on biomarkers identifying patients with mild cognitive impairment at highest risk for transitioning to Alzheimer's disease. Here, we applied recently developed analysis techniques to investigate cross-sectional differences in subcortical shape and volume alterations in patients with stable mild cognitive impairment (MCI) (n = 23, age range 59-82, 47.8% female), future converters at baseline (n = 10, age range 66-84, 90% female) and at time of conversion (age range 68-87) compared to group-wise age and gender matched healthy control subjects (n = 23, age range 61-81, 47.8% female; n = 10, age range 66-82, 80% female; n = 10, age range 68-82, 70% female). Additionally, we studied cortical thinning and global and local measures of hippocampal atrophy as known key imaging markers for Alzheimer's disease. Apart from bilateral striatal volume reductions, no morphometric alterations were found in cognitively stable patients. In contrast, we identified shape alterations in striatal and thalamic regions in future converters at baseline and at time of conversion. These shape alterations were paralleled by Alzheimer's disease like patterns of left hemispheric morphometric changes (cortical thinning in medial temporal regions, hippocampal total and subfield atrophy) in future converters at baseline with progression to similar right hemispheric alterations at time of conversion. Additionally, receiver operating characteristic curve analysis indicated that subcortical shape alterations may outperform hippocampal volume in identifying future converters at baseline. These results further confirm the key role of early cortical thinning and hippocampal atrophy in the early detection of Alzheimer's disease. But first and foremost, and by distinguishing future converters but not patients with stable cognitive abilities from cognitively normal subjects, our results support the value of early subcortical shape alterations and reduced hippocampal

  9. Subcortical Shape Changes, Hippocampal Atrophy and Cortical Thinning in Future Alzheimer's Disease Patients

    PubMed Central

    Kälin, Andrea M.; Park, Min T. M.; Chakravarty, M. Mallar; Lerch, Jason P.; Michels, Lars; Schroeder, Clemens; Broicher, Sarah D.; Kollias, Spyros; Nitsch, Roger M.; Gietl, Anton F.; Unschuld, Paul G.; Hock, Christoph; Leh, Sandra E.

    2017-01-01

    Efficacy of future treatments depends on biomarkers identifying patients with mild cognitive impairment at highest risk for transitioning to Alzheimer's disease. Here, we applied recently developed analysis techniques to investigate cross-sectional differences in subcortical shape and volume alterations in patients with stable mild cognitive impairment (MCI) (n = 23, age range 59–82, 47.8% female), future converters at baseline (n = 10, age range 66–84, 90% female) and at time of conversion (age range 68–87) compared to group-wise age and gender matched healthy control subjects (n = 23, age range 61–81, 47.8% female; n = 10, age range 66–82, 80% female; n = 10, age range 68–82, 70% female). Additionally, we studied cortical thinning and global and local measures of hippocampal atrophy as known key imaging markers for Alzheimer's disease. Apart from bilateral striatal volume reductions, no morphometric alterations were found in cognitively stable patients. In contrast, we identified shape alterations in striatal and thalamic regions in future converters at baseline and at time of conversion. These shape alterations were paralleled by Alzheimer's disease like patterns of left hemispheric morphometric changes (cortical thinning in medial temporal regions, hippocampal total and subfield atrophy) in future converters at baseline with progression to similar right hemispheric alterations at time of conversion. Additionally, receiver operating characteristic curve analysis indicated that subcortical shape alterations may outperform hippocampal volume in identifying future converters at baseline. These results further confirm the key role of early cortical thinning and hippocampal atrophy in the early detection of Alzheimer's disease. But first and foremost, and by distinguishing future converters but not patients with stable cognitive abilities from cognitively normal subjects, our results support the value of early subcortical shape alterations and reduced

  10. Subcortical origins of human and monkey neocortical interneurons.

    PubMed

    Ma, Tong; Wang, Congmin; Wang, Lei; Zhou, Xing; Tian, Miao; Zhang, Qiangqiang; Zhang, Yue; Li, Jiwen; Liu, Zhidong; Cai, Yuqun; Liu, Fang; You, Yan; Chen, Chao; Campbell, Kenneth; Song, Hongjun; Ma, Lan; Rubenstein, John L; Yang, Zhengang

    2013-11-01

    Cortical GABAergic inhibitory interneurons have crucial roles in the development and function of the cerebral cortex. In rodents, nearly all neocortical interneurons are generated from the subcortical ganglionic eminences. In humans and nonhuman primates, however, the developmental origin of neocortical GABAergic interneurons remains unclear. Here we show that the expression patterns of several key transcription factors in the developing primate telencephalon are very similar to those in rodents, delineating the three main subcortical progenitor domains (the medial, lateral and caudal ganglionic eminences) and the interneurons tangentially migrating from them. On the basis of the continuity of Sox6, COUP-TFII and Sp8 transcription factor expression and evidence from cell migration and cell fate analyses, we propose that the majority of primate neocortical GABAergic interneurons originate from ganglionic eminences of the ventral telencephalon. Our findings reveal that the mammalian neocortex shares basic rules for interneuron development, substantially reshaping our understanding of the origin and classification of primate neocortical interneurons.

  11. Subcortical motor circuit excitability during simple and choice reaction time.

    PubMed

    Maslovat, Dana; Carlsen, Anthony N; Franks, Ian M

    2012-06-01

    The purpose of the current study was to examine the relationship between movement preparation and excitability of subcortical motor circuits, as measured by the reflexive response to a startling acoustic stimulus. We compared the size and incidence of activation in the sternocleidomastoid (startle indicator) from participants completing either a simple or choice reaction time (RT) task. Consistent with predictions, results indicated that the startle reflex habituated after several presentations of the SAS for the choice RT group but not for the simple RT group, which we attributed to advance motor preparatory processes involved in a simple RT task. Additionally, when participants from the choice RT group were put into a simple RT condition, the startle reflex response returned to nonhabituated levels. We conclude that the increased corticospinal activation associated with advance preparation may also result in increased subcortical activation, accounting for the observed lack of habituation to a startling stimulus in simple RT.

  12. Parietal network underlying movement control: disturbances during subcortical electrostimulation.

    PubMed

    Almairac, Fabien; Herbet, Guillaume; Moritz-Gasser, Sylvie; Duffau, Hugues

    2014-07-01

    Our understanding of brain movement control has changed over the last two decades. Recent findings in the monkey and in humans have led to a parallel and interconnected network. Nevertheless, little is known about these networks. Here, we present two cases of patients with a parietal low-grade glioma. They underwent surgery under local anesthesia with cortical and subcortical mapping. For patient 1, subcortical electrostimulation immediately posterior to thalamocortical fibers induced movement disorders, with an inhibition of leg and arm movements medially and, more laterally, an acceleration of arm movement. For patient 2, electrostimulation of white matter immediately posterior to thalamocortical fibers induced an inhibition of both arm movement. It means that the detected fibers in the parietal lobe may be involved in the motor control modulation. They are distributed veil-like immediately posterior to thalamocortical pathways and could correspond to a fronto-parietal movement control subnetwork. These two cases highlight the major role of the subcortical connectivity in movement regulation, involving parietal lobe, thus the necessity to be identified and preserved during brain surgery.

  13. Methylphenidate and atomoxetine inhibit social play behavior through prefrontal and subcortical limbic mechanisms in rats.

    PubMed

    Achterberg, E J Marijke; van Kerkhof, Linda W M; Damsteegt, Ruth; Trezza, Viviana; Vanderschuren, Louk J M J

    2015-01-07

    Positive social interactions during the juvenile and adolescent phases of life, in the form of social play behavior, are important for social and cognitive development. However, the neural mechanisms of social play behavior remain incompletely understood. We have previously shown that methylphenidate and atomoxetine, drugs widely used for the treatment of attention-deficit hyperactivity disorder (ADHD), suppress social play in rats through a noradrenergic mechanism of action. Here, we aimed to identify the neural substrates of the play-suppressant effects of these drugs. Methylphenidate is thought to exert its effects on cognition and emotion through limbic corticostriatal systems. Therefore, methylphenidate was infused into prefrontal and orbitofrontal cortical regions as well as into several subcortical limbic areas implicated in social play. Infusion of methylphenidate into the anterior cingulate cortex, infralimbic cortex, basolateral amygdala, and habenula inhibited social play, but not social exploratory behavior or locomotor activity. Consistent with a noradrenergic mechanism of action of methylphenidate, infusion of the noradrenaline reuptake inhibitor atomoxetine into these same regions also reduced social play. Methylphenidate administration into the prelimbic, medial/ventral orbitofrontal, and ventrolateral orbitofrontal cortex, mediodorsal thalamus, or nucleus accumbens shell was ineffective. Our data show that the inhibitory effects of methylphenidate and atomoxetine on social play are mediated through a distributed network of prefrontal and limbic subcortical regions implicated in cognitive control and emotional processes. These findings increase our understanding of the neural underpinnings of this developmentally important social behavior, as well as the mechanism of action of two widely used treatments for ADHD.

  14. Small-World Brain Network and Dynamic Functional Distribution in Patients with Subcortical Vascular Cognitive Impairment

    PubMed Central

    Yu, Yongqiang; Zhou, Xia; Wang, Haibao; Hu, Xiaopeng; Zhu, Xiaoqun; Xu, Liyan; Zhang, Chao; Sun, Zhongwu

    2015-01-01

    To investigate the topological properties of the functional connectivity and their relationships with cognition impairment in subcortical vascular cognitive impairment (SVCI) patients, resting-state fMRI and graph theory approaches were employed in 23 SVCI patients and 20 healthy controls. Functional connectivity between 90 brain regions was estimated using bivariate correlation analysis and thresholded to construct a set of undirected graphs. Moreover, all of them were subjected to a battery of cognitive assessment, and the correlations between graph metrics and cognitive performance were further analyzed. Our results are as follows: functional brain networks of both SVCI patients and controls showed small-world attributes over a range of thresholds(0.15≤sparsity≤0.40). However, global topological organization of the functional brain networks in SVCI was significantly disrupted, as indicated by reduced global and local efficiency, clustering coefficients and increased characteristic path lengths relative to normal subjects. The decreased activity areas in SVCI predominantly targeted in the frontal-temporal lobes, while subcortical regions showed increased topological properties, which are suspected to compensate for the inefficiency of the functional network. We also demonstrated that altered brain network properties in SVCI are closely correlated with general cognitive and praxis dysfunction. The disruption of whole-brain topological organization of the functional connectome provides insight into the functional changes in the human brain in SVCI. PMID:26132397

  15. Timing predictability enhances regularity encoding in the human subcortical auditory pathway.

    PubMed

    Gorina-Careta, Natàlia; Zarnowiec, Katarzyna; Costa-Faidella, Jordi; Escera, Carles

    2016-11-17

    The encoding of temporal regularities is a critical property of the auditory system, as short-term neural representations of environmental statistics serve to auditory object formation and detection of potentially relevant novel stimuli. A putative neural mechanism underlying regularity encoding is repetition suppression, the reduction of neural activity to repeated stimulation. Although repetitive stimulation per se has shown to reduce auditory neural activity in animal cortical and subcortical levels and in the human cerebral cortex, other factors such as timing may influence the encoding of statistical regularities. This study was set out to investigate whether temporal predictability in the ongoing auditory input modulates repetition suppression in subcortical stages of the auditory processing hierarchy. Human auditory frequency-following responses (FFR) were recorded to a repeating consonant-vowel stimuli (/wa/) delivered in temporally predictable and unpredictable conditions. FFR amplitude was attenuated by repetition independently of temporal predictability, yet we observed an accentuated suppression when the incoming stimulation was temporally predictable. These findings support the view that regularity encoding spans across the auditory hierarchy and point to temporal predictability as a modulatory factor of regularity encoding in early stages of the auditory pathway.

  16. Timing predictability enhances regularity encoding in the human subcortical auditory pathway

    PubMed Central

    Gorina-Careta, Natàlia; Zarnowiec, Katarzyna; Costa-Faidella, Jordi; Escera, Carles

    2016-01-01

    The encoding of temporal regularities is a critical property of the auditory system, as short-term neural representations of environmental statistics serve to auditory object formation and detection of potentially relevant novel stimuli. A putative neural mechanism underlying regularity encoding is repetition suppression, the reduction of neural activity to repeated stimulation. Although repetitive stimulation per se has shown to reduce auditory neural activity in animal cortical and subcortical levels and in the human cerebral cortex, other factors such as timing may influence the encoding of statistical regularities. This study was set out to investigate whether temporal predictability in the ongoing auditory input modulates repetition suppression in subcortical stages of the auditory processing hierarchy. Human auditory frequency–following responses (FFR) were recorded to a repeating consonant–vowel stimuli (/wa/) delivered in temporally predictable and unpredictable conditions. FFR amplitude was attenuated by repetition independently of temporal predictability, yet we observed an accentuated suppression when the incoming stimulation was temporally predictable. These findings support the view that regularity encoding spans across the auditory hierarchy and point to temporal predictability as a modulatory factor of regularity encoding in early stages of the auditory pathway. PMID:27853313

  17. Thyroid Hormone-Dependent Formation of a Subcortical Band Heterotopia (SBH) in the Neonatal Brain is not Exacerbated Under Conditions of Low Dietary Iron

    EPA Science Inventory

    Thyroid hormones (TH) are critical for brain development. Modest TH insufficiency in pregnant rats induced by propylthiouracil (PTU) results in formation of a structural abnormality, a subcortical band heterotopia (SBH), in brains of offspring. PTU reduces TH by inhibiting the s...

  18. Anomalous subcortical morphology in boys, but not girls, with ADHD compared to typically developing controls and correlates with emotion dysregulation.

    PubMed

    Seymour, Karen E; Tang, Xiaoying; Crocetti, Deana; Mostofsky, Stewart H; Miller, Michael I; Rosch, Keri S

    2017-03-30

    There has been limited investigation of volume and shape difference in subcortical structures in children with ADHD and a paucity of examination of the influence of sex on these findings. The objective of this study was to examine morphology (volume and shape) of subcortical structures and their association with emotion dysregulation (ED) in girls and boys with ADHD as compared to their typically-developing (TD) counterparts. Participants included 218 children ages 8-12 years old with and without DSM-IV ADHD. Structural magnetic resonance images were obtained, and shape analyses were conducted using large deformation diffeomorphic metric mapping (LDDMM). Compared to TD boys, boys with ADHD showed reduced volumes in the bilateral globus pallidus and amygdala. There were no volumetric differences in any structure between ADHD and TD girls. Shape analysis revealed localized compressions within the globus pallidus, putamen and amygdala in ADHD boys relative to TD boys, as well as significant correlations between increased ED and unique subregion expansion in right globus pallidus, putamen, and right amygdala. Our findings suggest a sexually dimorphic pattern of differences in subcortical structures in children with ADHD compared to TD children, and a possible neurobiological mechanism by which boys with ADHD demonstrate increased difficulties with ED.

  19. Multi-infarct dementia, subcortical dementia, and hydrocephalus.

    PubMed

    Nadeau, S E

    1991-05-01

    The diagnostic evaluation of dementia is directed toward the identification of treatable causes. It can be facilitated by classification of the dementia into one of four categories: attentional, amnestic, cognitive, and intentional. Intentional dementia reflects dysfunction of frontal lobe systems, components of which include the frontal cortex, basal ganglia, thalamus, limbic structures, and subcortical white matter. Disorders that affect one or more of these components and produce intentional dementia include Binswanger's disease, Parkinson's disease, Huntington's disease, HIV infection, closed head injury, normal pressure hydrocephalus, neoplasms, syphilis, vitamin B12 deficiency, multiple sclerosis, and a number of uncommon degenerative and acquired syndromes. Depression may resemble intentional dementia. Guidelines for diagnosis and management are discussed.

  20. The subcortical maternal complex: multiple functions for one biological structure?

    PubMed

    Bebbere, D; Masala, L; Albertini, D F; Ledda, S

    2016-11-01

    The subcortical maternal complex (SCMC) is a multiprotein complex uniquely expressed in mammalian oocytes and early embryos, essential for zygote progression beyond the first embryonic cell divisions. Similiar to other factors encoded by maternal effect genes, the physiological role of SCMC remains unclear, although recent evidence has provided important molecular insights into different possible functions. Its potential involvement in human fertility is attracting increasing attention; however, the complete story is far from being told. The present mini review provides an overview of recent findings related to the SCMC and discusses its potential physiological role/s with the aim of inspiring new directions for future research.

  1. Distinct Genetic Influences on Cortical and Subcortical Brain Structures

    PubMed Central

    Wen, Wei; Thalamuthu, Anbupalam; Mather, Karen A.; Zhu, Wanlin; Jiang, Jiyang; de Micheaux, Pierre Lafaye; Wright, Margaret J.; Ames, David; Sachdev, Perminder S.

    2016-01-01

    This study examined the heritability of brain grey matter structures in a subsample of older adult twins (93 MZ and 68 DZ twin pairs; mean age 70 years) from the Older Australian Twins Study. The heritability estimates of subcortical regions ranged from 0.41 (amygdala) to 0.73 (hippocampus), and of cortical regions, from 0.55 (parietal lobe) to 0.78 (frontal lobe). Corresponding structures in the two hemispheres were influenced by the same genetic factors and high genetic correlations were observed between the two hemispheric regions. There were three genetically correlated clusters, comprising (i) the cortical lobes (frontal, temporal, parietal and occipital lobes); (ii) the basal ganglia (caudate, putamen and pallidum) with weak genetic correlations with cortical lobes, and (iii) the amygdala, hippocampus, thalamus and nucleus accumbens grouped together, which genetically correlated with both basal ganglia and cortical lobes, albeit relatively weakly. Our study demonstrates a complex but patterned and clustered genetic architecture of the human brain, with divergent genetic determinants of cortical and subcortical structures, in particular the basal ganglia. PMID:27595976

  2. Common genetic variants influence human subcortical brain structures.

    PubMed

    Hibar, Derrek P; Stein, Jason L; Renteria, Miguel E; Arias-Vasquez, Alejandro; Desrivières, Sylvane; Jahanshad, Neda; Toro, Roberto; Wittfeld, Katharina; Abramovic, Lucija; Andersson, Micael; Aribisala, Benjamin S; Armstrong, Nicola J; Bernard, Manon; Bohlken, Marc M; Boks, Marco P; Bralten, Janita; Brown, Andrew A; Chakravarty, M Mallar; Chen, Qiang; Ching, Christopher R K; Cuellar-Partida, Gabriel; den Braber, Anouk; Giddaluru, Sudheer; Goldman, Aaron L; Grimm, Oliver; Guadalupe, Tulio; Hass, Johanna; Woldehawariat, Girma; Holmes, Avram J; Hoogman, Martine; Janowitz, Deborah; Jia, Tianye; Kim, Sungeun; Klein, Marieke; Kraemer, Bernd; Lee, Phil H; Olde Loohuis, Loes M; Luciano, Michelle; Macare, Christine; Mather, Karen A; Mattheisen, Manuel; Milaneschi, Yuri; Nho, Kwangsik; Papmeyer, Martina; Ramasamy, Adaikalavan; Risacher, Shannon L; Roiz-Santiañez, Roberto; Rose, Emma J; Salami, Alireza; Sämann, Philipp G; Schmaal, Lianne; Schork, Andrew J; Shin, Jean; Strike, Lachlan T; Teumer, Alexander; van Donkelaar, Marjolein M J; van Eijk, Kristel R; Walters, Raymond K; Westlye, Lars T; Whelan, Christopher D; Winkler, Anderson M; Zwiers, Marcel P; Alhusaini, Saud; Athanasiu, Lavinia; Ehrlich, Stefan; Hakobjan, Marina M H; Hartberg, Cecilie B; Haukvik, Unn K; Heister, Angelien J G A M; Hoehn, David; Kasperaviciute, Dalia; Liewald, David C M; Lopez, Lorna M; Makkinje, Remco R R; Matarin, Mar; Naber, Marlies A M; McKay, D Reese; Needham, Margaret; Nugent, Allison C; Pütz, Benno; Royle, Natalie A; Shen, Li; Sprooten, Emma; Trabzuni, Daniah; van der Marel, Saskia S L; van Hulzen, Kimm J E; Walton, Esther; Wolf, Christiane; Almasy, Laura; Ames, David; Arepalli, Sampath; Assareh, Amelia A; Bastin, Mark E; Brodaty, Henry; Bulayeva, Kazima B; Carless, Melanie A; Cichon, Sven; Corvin, Aiden; Curran, Joanne E; Czisch, Michael; de Zubicaray, Greig I; Dillman, Allissa; Duggirala, Ravi; Dyer, Thomas D; Erk, Susanne; Fedko, Iryna O; Ferrucci, Luigi; Foroud, Tatiana M; Fox, Peter T; Fukunaga, Masaki; Gibbs, J Raphael; Göring, Harald H H; Green, Robert C; Guelfi, Sebastian; Hansell, Narelle K; Hartman, Catharina A; Hegenscheid, Katrin; Heinz, Andreas; Hernandez, Dena G; Heslenfeld, Dirk J; Hoekstra, Pieter J; Holsboer, Florian; Homuth, Georg; Hottenga, Jouke-Jan; Ikeda, Masashi; Jack, Clifford R; Jenkinson, Mark; Johnson, Robert; Kanai, Ryota; Keil, Maria; Kent, Jack W; Kochunov, Peter; Kwok, John B; Lawrie, Stephen M; Liu, Xinmin; Longo, Dan L; McMahon, Katie L; Meisenzahl, Eva; Melle, Ingrid; Mohnke, Sebastian; Montgomery, Grant W; Mostert, Jeanette C; Mühleisen, Thomas W; Nalls, Michael A; Nichols, Thomas E; Nilsson, Lars G; Nöthen, Markus M; Ohi, Kazutaka; Olvera, Rene L; Perez-Iglesias, Rocio; Pike, G Bruce; Potkin, Steven G; Reinvang, Ivar; Reppermund, Simone; Rietschel, Marcella; Romanczuk-Seiferth, Nina; Rosen, Glenn D; Rujescu, Dan; Schnell, Knut; Schofield, Peter R; Smith, Colin; Steen, Vidar M; Sussmann, Jessika E; Thalamuthu, Anbupalam; Toga, Arthur W; Traynor, Bryan J; Troncoso, Juan; Turner, Jessica A; Valdés Hernández, Maria C; van 't Ent, Dennis; van der Brug, Marcel; van der Wee, Nic J A; van Tol, Marie-Jose; Veltman, Dick J; Wassink, Thomas H; Westman, Eric; Zielke, Ronald H; Zonderman, Alan B; Ashbrook, David G; Hager, Reinmar; Lu, Lu; McMahon, Francis J; Morris, Derek W; Williams, Robert W; Brunner, Han G; Buckner, Randy L; Buitelaar, Jan K; Cahn, Wiepke; Calhoun, Vince D; Cavalleri, Gianpiero L; Crespo-Facorro, Benedicto; Dale, Anders M; Davies, Gareth E; Delanty, Norman; Depondt, Chantal; Djurovic, Srdjan; Drevets, Wayne C; Espeseth, Thomas; Gollub, Randy L; Ho, Beng-Choon; Hoffmann, Wolfgang; Hosten, Norbert; Kahn, René S; Le Hellard, Stephanie; Meyer-Lindenberg, Andreas; Müller-Myhsok, Bertram; Nauck, Matthias; Nyberg, Lars; Pandolfo, Massimo; Penninx, Brenda W J H; Roffman, Joshua L; Sisodiya, Sanjay M; Smoller, Jordan W; van Bokhoven, Hans; van Haren, Neeltje E M; Völzke, Henry; Walter, Henrik; Weiner, Michael W; Wen, Wei; White, Tonya; Agartz, Ingrid; Andreassen, Ole A; Blangero, John; Boomsma, Dorret I; Brouwer, Rachel M; Cannon, Dara M; Cookson, Mark R; de Geus, Eco J C; Deary, Ian J; Donohoe, Gary; Fernández, Guillén; Fisher, Simon E; Francks, Clyde; Glahn, David C; Grabe, Hans J; Gruber, Oliver; Hardy, John; Hashimoto, Ryota; Hulshoff Pol, Hilleke E; Jönsson, Erik G; Kloszewska, Iwona; Lovestone, Simon; Mattay, Venkata S; Mecocci, Patrizia; McDonald, Colm; McIntosh, Andrew M; Ophoff, Roel A; Paus, Tomas; Pausova, Zdenka; Ryten, Mina; Sachdev, Perminder S; Saykin, Andrew J; Simmons, Andy; Singleton, Andrew; Soininen, Hilkka; Wardlaw, Joanna M; Weale, Michael E; Weinberger, Daniel R; Adams, Hieab H H; Launer, Lenore J; Seiler, Stephan; Schmidt, Reinhold; Chauhan, Ganesh; Satizabal, Claudia L; Becker, James T; Yanek, Lisa; van der Lee, Sven J; Ebling, Maritza; Fischl, Bruce; Longstreth, W T; Greve, Douglas; Schmidt, Helena; Nyquist, Paul; Vinke, Louis N; van Duijn, Cornelia M; Xue, Luting; Mazoyer, Bernard; Bis, Joshua C; Gudnason, Vilmundur; Seshadri, Sudha; Ikram, M Arfan; Martin, Nicholas G; Wright, Margaret J; Schumann, Gunter; Franke, Barbara; Thompson, Paul M; Medland, Sarah E

    2015-04-09

    The highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and motivation, and altered circuits can lead to abnormal behaviour and disease. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume and intracranial volume. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 × 10(-33); 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability in human brain development, and may help to determine mechanisms of neuropsychiatric dysfunction.

  3. Subcortical connections of area V4 in the macaque

    PubMed Central

    Gattass, Ricardo; Galkin, Thelma W; Desimone, Robert; Ungerleider, Leslie G

    2014-01-01

    Area V4 has numerous, topographically organized connections with multiple cortical areas, some of which are important for spatially organized visual processing, and others which seem important for spatial attention. Although the topographic organization of V4’s connections with other cortical areas has been established, the detailed topography of its connections with subcortical areas is unclear. We therefore injected retrograde and anterograde tracers in different topographical regions of V4 in nine macaques to determine the organization of its subcortical connections. The injection sites included representations ranging from the fovea to far peripheral eccentricities in both the upper and lower visual fields. The topographically organized connections of V4 included bidirectional connections with four subdivisions of the pulvinar, two subdivisions of the claustrum, and the interlaminar portions of the lateral geniculate nucleus, and efferent projections to the superficial and intermediate layers of the superior colliculus, the thalamic reticular nucleus, and the caudate nucleus. All of these structures have a possible role in spatial attention. The nontopographic, or converging, connections included bidirectional connections with the lateral nucleus of the amygdala, afferent inputs from the dorsal raphe, median raphe, locus coeruleus, ventral tegmentum and nucleus basalis of Meynert, and efferent projections to the putamen. Any role of these structures in attention may be less spatially specific. J. Comp. Neurol. 522:1941–1965, 2014. PMID:24288173

  4. Age effect on subcortical structures in healthy adults

    PubMed Central

    Goodro, Matt; Sameti, Mohammad; Patenaude, Brian; Fein, George

    2012-01-01

    Cross-sectional age effects in normal control volunteers were investigated in 8 subcortical structures: lateral ventricles, thalamus, caudate, putamen, pallidum, hippocampus, amygdala and nucleus accumbens. Two hundred and twenty six control subjects, ranging in age from 19 to 85 years, were scanned on a 1.5T GE system (n = 184) or a 3.0T Siemens system (n = 42). Cranium-size adjusted subcortical structure volumes were estimated using FSL’s FIRST software, which is fully automated. Significant age effects were found for all volumes when the entire age range was analyzed, however the older subjects (60–85 years of age) showed a stronger correlation between age and structural volume for the ventricles, hippocampus, amygdala and accumbens than middle-aged (35–60 years of age) subjects. Middle-aged subjects were studied at both sites, and age effects in these groups were comparable, despite differences in magnet strength and acquisition systems. This agreement lends support to the validity of the image analysis tools and procedures used in the present study. PMID:22863654

  5. Common genetic variants influence human subcortical brain structures

    PubMed Central

    Hibar, Derrek P.; Stein, Jason L.; Renteria, Miguel E.; Arias-Vasquez, Alejandro; Desrivières, Sylvane; Jahanshad, Neda; Toro, Roberto; Wittfeld, Katharina; Abramovic, Lucija; Andersson, Micael; Aribisala, Benjamin S.; Armstrong, Nicola J.; Bernard, Manon; Bohlken, Marc M.; Boks, Marco P.; Bralten, Janita; Brown, Andrew A.; Chakravarty, M. Mallar; Chen, Qiang; Ching, Christopher R. K.; Cuellar-Partida, Gabriel; den Braber, Anouk; Giddaluru, Sudheer; Goldman, Aaron L.; Grimm, Oliver; Guadalupe, Tulio; Hass, Johanna; Woldehawariat, Girma; Holmes, Avram J.; Hoogman, Martine; Janowitz, Deborah; Jia, Tianye; Kim, Sungeun; Klein, Marieke; Kraemer, Bernd; Lee, Phil H.; Olde Loohuis, Loes M.; Luciano, Michelle; Macare, Christine; Mather, Karen A.; Mattheisen, Manuel; Milaneschi, Yuri; Nho, Kwangsik; Papmeyer, Martina; Ramasamy, Adaikalavan; Risacher, Shannon L.; Roiz-Santiañez, Roberto; Rose, Emma J.; Salami, Alireza; Sämann, Philipp G.; Schmaal, Lianne; Schork, Andrew J.; Shin, Jean; Strike, Lachlan T.; Teumer, Alexander; van Donkelaar, Marjolein M. J.; van Eijk, Kristel R.; Walters, Raymond K.; Westlye, Lars T.; Whelan, Christopher D.; Winkler, Anderson M.; Zwiers, Marcel P.; Alhusaini, Saud; Athanasiu, Lavinia; Ehrlich, Stefan; Hakobjan, Marina M. H.; Hartberg, Cecilie B.; Haukvik, Unn K.; Heister, Angelien J. G. A. M.; Hoehn, David; Kasperaviciute, Dalia; Liewald, David C. M.; Lopez, Lorna M.; Makkinje, Remco R. R.; Matarin, Mar; Naber, Marlies A. M.; McKay, D. Reese; Needham, Margaret; Nugent, Allison C.; Pütz, Benno; Royle, Natalie A.; Shen, Li; Sprooten, Emma; Trabzuni, Daniah; van der Marel, Saskia S. L.; van Hulzen, Kimm J. E.; Walton, Esther; Wolf, Christiane; Almasy, Laura; Ames, David; Arepalli, Sampath; Assareh, Amelia A.; Bastin, Mark E.; Brodaty, Henry; Bulayeva, Kazima B.; Carless, Melanie A.; Cichon, Sven; Corvin, Aiden; Curran, Joanne E.; Czisch, Michael; de Zubicaray, Greig I.; Dillman, Allissa; Duggirala, Ravi; Dyer, Thomas D.; Erk, Susanne; Fedko, Iryna O.; Ferrucci, Luigi; Foroud, Tatiana M.; Fox, Peter T.; Fukunaga, Masaki; Gibbs, J. Raphael; Göring, Harald H. H.; Green, Robert C.; Guelfi, Sebastian; Hansell, Narelle K.; Hartman, Catharina A.; Hegenscheid, Katrin; Heinz, Andreas; Hernandez, Dena G.; Heslenfeld, Dirk J.; Hoekstra, Pieter J.; Holsboer, Florian; Homuth, Georg; Hottenga, Jouke-Jan; Ikeda, Masashi; Jack, Clifford R.; Jenkinson, Mark; Johnson, Robert; Kanai, Ryota; Keil, Maria; Kent, Jack W.; Kochunov, Peter; Kwok, John B.; Lawrie, Stephen M.; Liu, Xinmin; Longo, Dan L.; McMahon, Katie L.; Meisenzahl, Eva; Melle, Ingrid; Mohnke, Sebastian; Montgomery, Grant W.; Mostert, Jeanette C.; Mühleisen, Thomas W.; Nalls, Michael A.; Nichols, Thomas E.; Nilsson, Lars G.; Nöthen, Markus M.; Ohi, Kazutaka; Olvera, Rene L.; Perez-Iglesias, Rocio; Pike, G. Bruce; Potkin, Steven G.; Reinvang, Ivar; Reppermund, Simone; Rietschel, Marcella; Romanczuk-Seiferth, Nina; Rosen, Glenn D.; Rujescu, Dan; Schnell, Knut; Schofield, Peter R.; Smith, Colin; Steen, Vidar M.; Sussmann, Jessika E.; Thalamuthu, Anbupalam; Toga, Arthur W.; Traynor, Bryan J.; Troncoso, Juan; Turner, Jessica A.; Valdés Hernández, Maria C.; van ’t Ent, Dennis; van der Brug, Marcel; van der Wee, Nic J. A.; van Tol, Marie-Jose; Veltman, Dick J.; Wassink, Thomas H.; Westman, Eric; Zielke, Ronald H.; Zonderman, Alan B.; Ashbrook, David G.; Hager, Reinmar; Lu, Lu; McMahon, Francis J.; Morris, Derek W.; Williams, Robert W.; Brunner, Han G.; Buckner, Randy L.; Buitelaar, Jan K.; Cahn, Wiepke; Calhoun, Vince D.; Cavalleri, Gianpiero L.; Crespo-Facorro, Benedicto; Dale, Anders M.; Davies, Gareth E.; Delanty, Norman; Depondt, Chantal; Djurovic, Srdjan; Drevets, Wayne C.; Espeseth, Thomas; Gollub, Randy L.; Ho, Beng-Choon; Hoffmann, Wolfgang; Hosten, Norbert; Kahn, René S.; Le Hellard, Stephanie; Meyer-Lindenberg, Andreas; Müller-Myhsok, Bertram; Nauck, Matthias; Nyberg, Lars; Pandolfo, Massimo; Penninx, Brenda W. J. H.; Roffman, Joshua L.; Sisodiya, Sanjay M.; Smoller, Jordan W.; van Bokhoven, Hans; van Haren, Neeltje E. M.; Völzke, Henry; Walter, Henrik; Weiner, Michael W.; Wen, Wei; White, Tonya; Agartz, Ingrid; Andreassen, Ole A.; Blangero, John; Boomsma, Dorret I.; Brouwer, Rachel M.; Cannon, Dara M.; Cookson, Mark R.; de Geus, Eco J. C.; Deary, Ian J.; Donohoe, Gary; Fernández, Guillén; Fisher, Simon E.; Francks, Clyde; Glahn, David C.; Grabe, Hans J.; Gruber, Oliver; Hardy, John; Hashimoto, Ryota; Hulshoff Pol, Hilleke E.; Jönsson, Erik G.

    2015-01-01

    The highly complex structure of the human brain is strongly shaped by genetic influences1. Subcortical brain regions form circuits with cortical areas to coordinate movement2, learning, memory3 and motivation4, and altered circuits can lead to abnormal behaviour and disease2. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume5 and intracranial volume6. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 × 10−33; 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability inhuman brain development, and may help to determine mechanisms of neuropsychiatric dysfunction. PMID:25607358

  6. Subcortical regional morphology correlates with fluid and spatial intelligence.

    PubMed

    Burgaleta, Miguel; MacDonald, Penny A; Martínez, Kenia; Román, Francisco J; Álvarez-Linera, Juan; Ramos González, Ana; Karama, Sherif; Colom, Roberto

    2014-05-01

    Neuroimaging studies have revealed associations between intelligence and brain morphology. However, researchers have focused primarily on the anatomical features of the cerebral cortex, whereas subcortical structures, such as the basal ganglia (BG), have often been neglected despite extensive functional evidence on their relation with higher-order cognition. Here we performed shape analyses to understand how individual differences in BG local morphology account for variability in cognitive performance. Structural MRI was acquired in 104 young adults (45 men, 59 women, mean age = 19.83, SD = 1.64), and the outer surface of striatal structures (caudate, nucleus accumbens, and putamen), globus pallidus, and thalamus was estimated for each subject and hemisphere. Further, nine cognitive tests were used to measure fluid (Gf), crystallized (Gc), and spatial intelligence (Gv). Latent scores for these factors were computed by means of confirmatory factor analysis and regressed vertex-wise against subcortical shape (local displacements of vertex position), controlling for age, sex, and adjusted for brain size. Significant results (FDR < 5%) were found for Gf and Gv, but not Gc, for the right striatal structures and thalamus. The main results show a relative enlargement of the rostral putamen, which is functionally connected to the right dorsolateral prefrontal cortex and other intelligence-related prefrontal areas.

  7. Derivative of wheat germ agglutinin specifically inhibits formyl-peptide-induced polymorphonuclear leukocyte chemotaxis by blocking re-expression (or recycling) of receptors

    SciTech Connect

    Perez, H.D.; Elfman, F.; Lobo, E.; Sklar, L.; Chenoweth, D.; Hooper, C.

    1986-03-01

    The mechanism of action of a derivative of wheat germ agglutinin (WGA-D) which specifically and irreversibly inhibits N-formyl-methionyl-leucyl-phenylalanine (FMLP)-induced polymorphonuclear leukocyte (PMN) chemotaxis was examined. At a concentration that completely inhibited PMN chemotaxis, WGA-D had no effect on either the uptake or release of (/sup 3/H)-FMLP by PMN. Similarly, WGA-D did not affect either the short-term binding to, or internalization by, PMN of a fluoresceinated FMLP analog. WGA-D did interfere, however, with the re-expression (or recycling) of FMLP receptors by PMN that had been preincubated with 1 ..mu..M FMLP for 10 min at 4/sup 0/C. This effect was specific for WGA-D, because it was not observed when concanavalin A was used. Scatchard plot analysis of FMLP binding to PMN after receptor re-expression demonstrated that WGA-D-treated PMN had a significant diminution in the number of high affinity receptors. WGA-D-mediated inhibition of FMLP receptor re-expression was associated with inhibition of FMLP-induced PMN chemotaxis, but had no effect on either FMLP-induced PMN superoxide anion generation or degranulation. Studies using (/sup 12/%I)-WGA-D demonstrated that PMN did not internalize WGA-D spontaneously. The data indicate that WGA-D perhaps by binding to the FMLP receptor, inhibits FMLP-induced PMN chemotaxis by blocking the re-expression (or recycling) of a population of receptors required for continuous migration.

  8. 21 CFR 882.5840 - Implanted intracerebral/subcortical stimulator for pain relief.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... pain relief. 882.5840 Section 882.5840 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... Devices § 882.5840 Implanted intracerebral/subcortical stimulator for pain relief. (a) Identification. An implanted intracerebral/subcortical stimulator for pain relief is a device that applies electrical...

  9. 21 CFR 882.5840 - Implanted intracerebral/subcortical stimulator for pain relief.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... pain relief. 882.5840 Section 882.5840 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... Devices § 882.5840 Implanted intracerebral/subcortical stimulator for pain relief. (a) Identification. An implanted intracerebral/subcortical stimulator for pain relief is a device that applies electrical...

  10. 21 CFR 882.5840 - Implanted intracerebral/subcortical stimulator for pain relief.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... pain relief. 882.5840 Section 882.5840 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... Devices § 882.5840 Implanted intracerebral/subcortical stimulator for pain relief. (a) Identification. An implanted intracerebral/subcortical stimulator for pain relief is a device that applies electrical...

  11. 21 CFR 882.5840 - Implanted intracerebral/subcortical stimulator for pain relief.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... pain relief. 882.5840 Section 882.5840 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... Devices § 882.5840 Implanted intracerebral/subcortical stimulator for pain relief. (a) Identification. An implanted intracerebral/subcortical stimulator for pain relief is a device that applies electrical...

  12. 21 CFR 882.5840 - Implanted intracerebral/subcortical stimulator for pain relief.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... pain relief. 882.5840 Section 882.5840 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... Devices § 882.5840 Implanted intracerebral/subcortical stimulator for pain relief. (a) Identification. An implanted intracerebral/subcortical stimulator for pain relief is a device that applies electrical...

  13. Mapping Subcortical Brain Maturation during Adolescence: Evidence of Hemisphere-and Sex-Specific Longitudinal Changes

    ERIC Educational Resources Information Center

    Dennison, Meg; Whittle, Sarah; Yücel, Murat; Vijayakumar, Nandita; Kline, Alexandria; Simmons, Julian; Allen, Nicholas B.

    2013-01-01

    Early to mid-adolescence is an important developmental period for subcortical brain maturation, but longitudinal studies of these neurodevelopmental changes are lacking. The present study acquired repeated magnetic resonance images from 60 adolescent subjects (28 female) at ages 12.5 and 16.5 years to map changes in subcortical structure volumes.…

  14. Consensus statement for diagnosis of subcortical small vessel disease

    PubMed Central

    Wallin, Anders; Wardlaw, Joanna M; Markus, Hugh S; Montaner, Joan; Wolfson, Leslie; Iadecola, Costantino; Zlokovic, Berislav V; Joutel, Anne; Dichgans, Martin; Duering, Marco; Schmidt, Reinhold; Korczyn, Amos D; Grinberg, Lea T; Chui, Helena C; Hachinski, Vladimir

    2016-01-01

    Vascular cognitive impairment (VCI) is the diagnostic term used to describe a heterogeneous group of sporadic and hereditary diseases of the large and small blood vessels. Subcortical small vessel disease (SVD) leads to lacunar infarcts and progressive damage to the white matter. Patients with progressive damage to the white matter, referred to as Binswanger’s disease (BD), constitute a spectrum from pure vascular disease to a mixture with neurodegenerative changes. Binswanger’s disease patients are a relatively homogeneous subgroup with hypoxic hypoperfusion, lacunar infarcts, and inflammation that act synergistically to disrupt the blood–brain barrier (BBB) and break down myelin. Identification of this subgroup can be facilitated by multimodal disease markers obtained from clinical, cerebrospinal fluid, neuropsychological, and imaging studies. This consensus statement identifies a potential set of biomarkers based on underlying pathologic changes that could facilitate diagnosis and aid patient selection for future collaborative treatment trials. PMID:26198175

  15. [Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)].

    PubMed

    Chen, Yun-Chung; Hsiao, Cheng-Tsung; Soong, Bing-Wen; Lee, Yi-Chung

    2014-06-01

    Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most prevalent monogenic cerebral small vessel diseases caused by a mutation in the NOTCH3 gene. The clinical manifestations of CADASIL range from single or multiple lacunar infarcts, transient ischemic attacks, dementia, migraine with aura to psychiatric disorders. The features of brain MRI of CADASIL include multiple lacunar infarcts and diffuse leukoencephalopathy, which frequently involves external capsules and anterior temporal regions. Almost all patients with CADASIL harbor cysteine-involving mutations in NOTCH3. In Taiwan, two thirds of CADASIL patients carry NOTCH3 p.R544C mutations, and only approximately 56% of patients with CADASIL have leukoencephalopathy with anterior temporal regions involvement.

  16. The influence of puberty on subcortical brain development.

    PubMed

    Goddings, Anne-Lise; Mills, Kathryn L; Clasen, Liv S; Giedd, Jay N; Viner, Russell M; Blakemore, Sarah-Jayne

    2014-03-01

    Puberty is characterized by hormonal, physical and psychological transformation. The human brain undergoes significant changes between childhood and adulthood, but little is known about how puberty influences its structural development. Using a longitudinal sample of 711 magnetic resonance imaging scans from 275 individuals aged 7-20years, we examined how subcortical brain regions change in relation to puberty. Our regions of interest included the amygdala, hippocampus and corpus striatum including the nucleus accumbens (NA), caudate, putamen and globus pallidus (GP). Pubertal development was significantly related to structural volume in all six regions in both sexes. Pubertal development and age had both independent and interactive influences on volume for the amygdala, hippocampus and putamen in both sexes, and the caudate in females. There was an interactive puberty-by-age effect on volume for the NA and GP in both sexes, and the caudate in males. These findings suggest a significant role for puberty in structural brain development.

  17. Subcortical intelligence: caudate volume predicts IQ in healthy adults.

    PubMed

    Grazioplene, Rachael G; G Ryman, Sephira; Gray, Jeremy R; Rustichini, Aldo; Jung, Rex E; DeYoung, Colin G

    2015-04-01

    This study examined the association between size of the caudate nuclei and intelligence. Based on the central role of the caudate in learning, as well as neuroimaging studies linking greater caudate volume to better attentional function, verbal ability, and dopamine receptor availability, we hypothesized the existence of a positive association between intelligence and caudate volume in three large independent samples of healthy adults (total N = 517). Regression of IQ onto bilateral caudate volume controlling for age, sex, and total brain volume indicated a significant positive correlation between caudate volume and intelligence, with a comparable magnitude of effect across each of the three samples. No other subcortical structures were independently associated with IQ, suggesting a specific biological link between caudate morphology and intelligence.

  18. A New MRI-Based Pediatric Subcortical Segmentation Technique (PSST).

    PubMed

    Loh, Wai Yen; Connelly, Alan; Cheong, Jeanie L Y; Spittle, Alicia J; Chen, Jian; Adamson, Christopher; Ahmadzai, Zohra M; Fam, Lillian Gabra; Rees, Sandra; Lee, Katherine J; Doyle, Lex W; Anderson, Peter J; Thompson, Deanne K

    2016-01-01

    Volumetric and morphometric neuroimaging studies of the basal ganglia and thalamus in pediatric populations have utilized existing automated segmentation tools including FIRST (Functional Magnetic Resonance Imaging of the Brain's Integrated Registration and Segmentation Tool) and FreeSurfer. These segmentation packages, however, are mostly based on adult training data. Given that there are marked differences between the pediatric and adult brain, it is likely an age-specific segmentation technique will produce more accurate segmentation results. In this study, we describe a new automated segmentation technique for analysis of 7-year-old basal ganglia and thalamus, called Pediatric Subcortical Segmentation Technique (PSST). PSST consists of a probabilistic 7-year-old subcortical gray matter atlas (accumbens, caudate, pallidum, putamen and thalamus) combined with a customized segmentation pipeline using existing tools: ANTs (Advanced Normalization Tools) and SPM (Statistical Parametric Mapping). The segmentation accuracy of PSST in 7-year-old data was compared against FIRST and FreeSurfer, relative to manual segmentation as the ground truth, utilizing spatial overlap (Dice's coefficient), volume correlation (intraclass correlation coefficient, ICC) and limits of agreement (Bland-Altman plots). PSST achieved spatial overlap scores ≥90% and ICC scores ≥0.77 when compared with manual segmentation, for all structures except the accumbens. Compared with FIRST and FreeSurfer, PSST showed higher spatial overlap (p FDR  < 0.05) and ICC scores, with less volumetric bias according to Bland-Altman plots. PSST is a customized segmentation pipeline with an age-specific atlas that accurately segments typical and atypical basal ganglia and thalami at age 7 years, and has the potential to be applied to other pediatric datasets.

  19. Cortical and subcortical mechanisms of brain-machine interfaces.

    PubMed

    Marchesotti, Silvia; Martuzzi, Roberto; Schurger, Aaron; Blefari, Maria Laura; Del Millán, José R; Bleuler, Hannes; Blanke, Olaf

    2017-03-21

    Technical advances in the field of Brain-Machine Interfaces (BMIs) enable users to control a variety of external devices such as robotic arms, wheelchairs, virtual entities and communication systems through the decoding of brain signals in real time. Most BMI systems sample activity from restricted brain regions, typically the motor and premotor cortex, with limited spatial resolution. Despite the growing number of applications, the cortical and subcortical systems involved in BMI control are currently unknown at the whole-brain level. Here, we provide a comprehensive and detailed report of the areas active during on-line BMI control. We recorded functional magnetic resonance imaging (fMRI) data while participants controlled an EEG-based BMI inside the scanner. We identified the regions activated during BMI control and how they overlap with those involved in motor imagery (without any BMI control). In addition, we investigated which regions reflect the subjective sense of controlling a BMI, the sense of agency for BMI-actions. Our data revealed an extended cortical-subcortical network involved in operating a motor-imagery BMI. This includes not only sensorimotor regions but also the posterior parietal cortex, the insula and the lateral occipital cortex. Interestingly, the basal ganglia and the anterior cingulate cortex were involved in the subjective sense of controlling the BMI. These results inform basic neuroscience by showing that the mechanisms of BMI control extend beyond sensorimotor cortices. This knowledge may be useful for the development of BMIs that offer a more natural and embodied feeling of control for the user. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

  20. Early neurone loss in Alzheimer's disease: cortical or subcortical?

    PubMed

    Arendt, Thomas; Brückner, Martina K; Morawski, Markus; Jäger, Carsten; Gertz, Hermann-Josef

    2015-02-10

    Alzheimer's disease (AD) is a degenerative disorder where the distribution of pathology throughout the brain is not random but follows a predictive pattern used for pathological staging. While the involvement of defined functional systems is fairly well established for more advanced stages, the initial sites of degeneration are still ill defined. The prevailing concept suggests an origin within the transentorhinal and entorhinal cortex (EC) from where pathology spreads to other areas. Still, this concept has been challenged recently suggesting a potential origin of degeneration in nonthalamic subcortical nuclei giving rise to cortical innervation such as locus coeruleus (LC) and nucleus basalis of Meynert (NbM). To contribute to the identification of the early site of degeneration, here, we address the question whether cortical or subcortical degeneration occurs more early and develops more quickly during progression of AD. To this end, we stereologically assessed neurone counts in the NbM, LC and EC layer-II in the same AD patients ranging from preclinical stages to severe dementia. In all three areas, neurone loss becomes detectable already at preclinical stages and is clearly manifest at prodromal AD/MCI. At more advanced AD, cell loss is most pronounced in the NbM > LC > layer-II EC. During early AD, however, the extent of cell loss is fairly balanced between all three areas without clear indications for a preference of one area. We can thus not rule out that there is more than one way of spreading from its site of origin or that degeneration even occurs independently at several sites in parallel.

  1. Subcortical ischemic vascular disease: Roles of oligodendrocyte function in experimental models of subcortical white-matter injury.

    PubMed

    Shindo, Akihiro; Liang, Anna C; Maki, Takakuni; Miyamoto, Nobukazu; Tomimoto, Hidekazu; Lo, Eng H; Arai, Ken

    2016-01-01

    Oligodendrocytes are one of the major cell types in cerebral white matter. Under normal conditions, they form myelin sheaths that encircle axons to support fast nerve conduction. Under conditions of cerebral ischemia, oligodendrocytes tend to die, resulting in white-matter dysfunction. Repair of white matter involves the ability of oligodendrocyte precursors to proliferate and mature. However, replacement of lost oligodendrocytes may not be the only mechanism for white-matter recovery. Emerging data now suggest that coordinated signaling between neural, glial, and vascular cells in the entire neurovascular unit may be required. In this mini-review, we discuss how oligodendrocyte lineage cells participate in signaling and crosstalk with other cell types to underlie function and recovery in various experimental models of subcortical white-matter injury.

  2. Subcortical ischemic vascular disease: Roles of oligodendrocyte function in experimental models of subcortical white-matter injury

    PubMed Central

    Shindo, Akihiro; Liang, Anna C; Maki, Takakuni; Miyamoto, Nobukazu; Tomimoto, Hidekazu; Lo, Eng H

    2016-01-01

    Oligodendrocytes are one of the major cell types in cerebral white matter. Under normal conditions, they form myelin sheaths that encircle axons to support fast nerve conduction. Under conditions of cerebral ischemia, oligodendrocytes tend to die, resulting in white-matter dysfunction. Repair of white matter involves the ability of oligodendrocyte precursors to proliferate and mature. However, replacement of lost oligodendrocytes may not be the only mechanism for white-matter recovery. Emerging data now suggest that coordinated signaling between neural, glial, and vascular cells in the entire neurovascular unit may be required. In this mini-review, we discuss how oligodendrocyte lineage cells participate in signaling and crosstalk with other cell types to underlie function and recovery in various experimental models of subcortical white-matter injury. PMID:25920960

  3. SUBCORTICAL CONNECTIONS OF THE PERIRHINAL, POSTRHINAL, AND ENTORHINAL CORTICES OF THE RAT. I. AFFERENTS

    PubMed Central

    Pereira, Inês Tomás; Agster, Kara L.; Burwell, Rebecca D.

    2016-01-01

    In this study we characterized the subcortical afferents for the rat PER areas 35 and 36, POR, and the lateral and medial entorhinal areas (LEA and MEA). We analyzed 33 retrograde tract-tracing experiments distributed across the five regions. For each experiment, we estimated the total numbers, percentages, and densities of labeled cells in 36 subcortical structures and nuclei distributed across septum, basal ganglia, claustrum, amygdala, olfactory structures, thalamus, and hypothalamus. We found that the complement of subcortical inputs differs across the five regions, especially the PER and POR. The PER receives input from the reuniens, suprageniculate, and medial geniculate thalamic nuclei as well as the amygdala. Overall, the subcortical inputs to the PER are consistent with a role in perception, multimodal processing, and the formation of associations that include the motivational significance of individual items and objects. Subcortical inputs to the POR were dominated by the dorsal thalamus, particularly the lateral posterior nucleus, a region implicated in visuospatial attention. The complement of subcortical inputs to the POR is consistent with a role in representing and monitoring the local spatial context. We also report that, in addition to the PER, the LEA and the medial band of the MEA also receive strong amygdala input. In contrast, subcortical input to the POR and the MEA lateral band includes much less amygdala input and is dominated by dorsal thalamic nuclei, particularly nuclei involved in spatial information processing. Like the cortical inputs, the patterns of subcortical inputs to these regions are consistent both with the view that the dorsal hippocampus is important for spatial cognition and the ventral hippocampus is important for affective cognition, and the view that they provide considerable functional integration. We conclude that the patterns of subcortical inputs to the PER, POR, and the entorhinal LEA and MEA provide further evidence

  4. Asymmetries of visual attention after circumscribed subcortical vascular lesions

    PubMed Central

    Fimm, B; Zahn, R; Mull, M; Kemeny, S; Buchwald, F; Block, F; Schwarz, M

    2001-01-01

    OBJECTIVE—To investigate the role of the basal ganglia and the thalamus for basic processes of visuospatial attention
METHODS—Fifteen patients with acute circumscribed vascular lesions (10 with haemorrhage and five with infarction) were included in the study. The lesions were confined exclusively to subcortical structures, such as the basal ganglia, internal capsule, and thalamus, which was confirmed by initial CT on the day of referral and MRI taken 14-28 days after clinical onset. These patients were examined with two computerised attentional tasks (one detection and one search task) measuring spatial visual attention.
RESULTS—There was a clear attentional asymmetry in patients with right hemispheric lesions (RHLs) in the visual search task. Seven out of eight patients with RHLs tended to be slower and/or missed significantly more target stimuli in the left sided part of a stimulus array consisting of 25 small squares than in right sided parts, although none of these patients showed signs of visual hemineglect in the visual detection task presenting visual information simultaneously to the right and left visual hemispace. All but one of these patients showed lesions in the posterior limb of the internal capsule and the putamen. On the other hand, patients with left hemispheric lesions were not impaired in the search task with only one patient showing more contralesional omissions of target stimuli than could be expected from the behaviour of normal controls.
CONCLUSIONS—The results are in line with previous results showing a dominant role of right hemispheric neuronal structures for spatial attention. Furthermore, the data suggest that even with right hemispheric subcortical lesions without cortical involvement deficits in spatial orienting of attention to the left hemispace can be seen. These asymmetries of visual attention in the absence of neglect symptoms are supposed to be caused (1) by a disruption of the motor corticostriato

  5. Cortical and subcortical patterns of synaptophysinlike immunoreactivity in Alzheimer's disease.

    PubMed Central

    Masliah, E.; Terry, R. D.; Alford, M.; DeTeresa, R.; Hansen, L. A.

    1991-01-01

    Quantification of synaptophysinlike immunoreactivity is a valuable method for studying the presynaptic terminals in the normal and damaged nervous system. The present report shows that in the control brain, the predominant pattern of synaptic immunostaining in the neocortex was that of an evenly distributed densely granular immunolabeling of the neuropil, while in the paleocortex and in subcortical areas of the brain most of the presynaptic terminals were distributed along the dendritic arborizations or around the neuronal somata. The immunochemical and the immunohistochemical analysis of the Alzheimer's disease tissue showed that the frontal and parietal cortex presented the most severe and widespread loss, with a 45% loss in synaptophysin immunoreactivity. These areas showed an average 35% loss of large neurons. The visual cortex, hippocampus, entorhinal cortex, nucleus basalis of Meynert, and locus ceruleus displayed some degree of loss, but to a lesser extent. In addition to this loss, the basic patterns of organization of the presynaptic terminals were altered, with the presence of abundant, enlarged synaptophysin-labeled terminals. This study further supports the role of synaptic pathology in Alzheimer's disease. Images Figure 10 Figure 11 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 12 PMID:1899001

  6. Subcortical correlates of auditory perceptual organization in humans.

    PubMed

    Yamagishi, Shimpei; Otsuka, Sho; Furukawa, Shigeto; Kashino, Makio

    2016-09-01

    To make sense of complex auditory scenes, the auditory system sequentially organizes auditory components into perceptual objects or streams. In the conventional view of this process, the cortex plays a major role in perceptual organization, and subcortical mechanisms merely provide the cortex with acoustical features. Here, we show that the neural activities of the brainstem are linked to perceptual organization, which alternates spontaneously for human listeners without any stimulus change. The stimulus used in the experiment was an unchanging sequence of repeated triplet tones, which can be interpreted as either one or two streams. Listeners were instructed to report the perceptual states whenever they experienced perceptual switching between one and two streams throughout the stimulus presentation. Simultaneously, we recorded event related potentials with scalp electrodes. We measured the frequency-following response (FFR), which is considered to originate from the brainstem. We also assessed thalamo-cortical activity through the middle-latency response (MLR). The results demonstrate that the FFR and MLR varied with the state of auditory stream perception. In addition, we found that the MLR change precedes the FFR change with perceptual switching from a one-stream to a two-stream percept. This suggests that there are top-down influences on brainstem activity from the thalamo-cortical pathway. These findings are consistent with the idea of a distributed, hierarchical neural network for perceptual organization and suggest that the network extends to the brainstem level.

  7. Subcortical orientation biases explain orientation selectivity of visual cortical cells

    PubMed Central

    Vidyasagar, Trichur R; Jayakumar, Jaikishan; Lloyd, Errol; Levichkina, Ekaterina V

    2015-01-01

    The primary visual cortex of carnivores and primates shows an orderly progression of domains of neurons that are selective to a particular orientation of visual stimuli such as bars and gratings. We recorded from single-thalamic afferent fibers that terminate in these domains to address the issue whether the orientation sensitivity of these fibers could form the basis of the remarkable orientation selectivity exhibited by most cortical cells. We first performed optical imaging of intrinsic signals to obtain a map of orientation domains on the dorsal aspect of the anaesthetized cat's area 17. After confirming using electrophysiological recordings the orientation preferences of single neurons within one or two domains in each animal, we pharmacologically silenced the cortex to leave only the afferent terminals active. The inactivation of cortical neurons was achieved by the superfusion of either kainic acid or muscimol. Responses of single geniculate afferents were then recorded by the use of high impedance electrodes. We found that the orientation preferences of the afferents matched closely with those of the cells in the orientation domains that they terminated in (Pearson's r = 0.633, n = 22, P = 0.002). This suggests a possible subcortical origin for cortical orientation selectivity. PMID:25855249

  8. Subcortical Band Heterotopia (SBH) in Rat Offspring Following Maternal Hypothyroxinemia: Structural and Functional Characteristics

    EPA Science Inventory

    Thyroid hormones (TH) play crucial roles in brain maturation, neuronal migration, and neocortical lamination. Subcortical band heterotopia (SBH) represent a class of neuronal migration errors in humans that are often associated with childhood epilepsy. We have previously reported...

  9. Subcortical deafferentation impairs behavioral reinforcement of long-term potentiation in the dentate gyrus of freely moving rats.

    PubMed

    Almaguer-Melian, W; Rosillo, J C; Frey, J U; Bergado, J A

    2006-01-01

    Long-term potentiation is a form of neural functional plasticity which has been related with memory formation and recovery of function after brain injury. Previous studies have shown that a transient early-long-term potentiation can be prolonged by direct stimulation of distinct brain areas, or behavioral stimuli with a high motivational content. The basolateral amygdala and other subcortical structures, like the medial septum and the locus coeruleus, are involved in mediating the reinforcing effect. We have previously shown that the lesion of the fimbria-fornix--the main entrance of subcortical afferents to the hippocampus--abolishes the reinforcing basolateral amygdala-effects on long-term potentiation in the dentate gyrus in vivo. It remains to be investigated, however, if such subcortical afferents may also be important for behavioral reinforcement of long-term potentiation. Young-adult (8 weeks) Sprague-Dawley male rats were fimbria-fornix-transected under anesthesia, and electrodes were implanted at the dentate gyrus and the perforant path. One week after surgery the freely moving animals were studied. Fimbria-fornix-lesion reduced the ability of the animals to develop long-term potentiation when a short pulse duration was used for tetanization (0.1 ms per half-wave of a biphasic stimulus), whereas increasing the pulse duration to 0.2 ms per half-wave during tetanization resulted in a transient early-long-term potentiation lasting about 4 h in the lesioned animals, comparable to that obtained in non-lesioned or sham-operated control rats. In water-deprived (24 h) control animals, i.e. in non-lesioned and sham-operated rats, early-long-term potentiation could be behaviorally reinforced by drinking 15 min after tetanization. However, in fimbria-fornix-lesioned animals long-term potentiation-reinforcement by drinking was not detected. This result indicates that the effect of behavioral-motivational stimuli to reinforce long-term potentiation is mediated by

  10. Regional cerebral blood flow and blood volume in patients with subcortical arteriosclerotic encephalopathy (SAE).

    PubMed

    Gückel, Friedemann J; Brix, Gunnar; Hennerici, Michael; Lucht, Robert; Ueltzhöffer, Christine; Neff, Wolfgang

    2007-10-01

    The aim of the present study was a detailed analysis of the regional cerebral blood flow and blood volume in patients with subcortical arteriosclerotic encephalopathy (SAE) by means of functional magnetic resonance imaging (MRI). A group of 26 patients with SAE and a group of 16 age-matched healthy volunteers were examined. Using a well-established dynamic susceptibility contrast-enhanced MRI method, the regional cerebral blood flow (rCBF) and blood volume (rCBV) were quantified for each subject in 12 different regions in the brain parenchyma. As compared to healthy volunteers, patients with SAE showed significantly reduced rCBF and rCBV values in white matter regions and in the occipital cortex. Regions containing predominantly grey matter show almost normal rCBF and rCBV values. In conclusion, quantitative analysis of rCBF and rCBV values demonstrates clearly that SAE is a disease that is associated with a reduced microcirculation predominantly in white matter.

  11. Ictal electrographic pattern of focal subcortical seizures induced by sound in rats.

    PubMed

    Vinogradova, Lyudmila V; Grinenko, Olesya A

    2016-03-15

    It is now recognized that both generalized and focal seizures may originate in subcortical structures. The well-known types of focal subcortically-driven seizures are gelastic seizures in patients with the hypothalamic hamartoma and sound-induced seizures in rodents with audiogenic epilepsy. The seizures are generated by subcortical intrinsically epileptogenic focus, the hamartoma in humans and the inferior colliculus (IC) in rodents. In patients with gelastic epilepsy additional seizure types may develop with time that are supposed to result from secondary epileptogenesis and spreading of epileptic discharges to the cortex. Repeated audiogenic seizures can also lead to development of additional seizure behavior and secondary epileptic activation of the cortex. This process, named audiogenic kindling, may be useful for studying secondary subcortico-cortical epileptogenesis. Using intracollicular and intracortical recordings, we studied an ictal electrographic pattern of focal subcortical seizures induced by repeated sound stimulation in Wistar audiogenic-susceptible rats. The audiogenic seizures, representing brief attacks of paroxysmal unidirectional running, were accompanied by epileptiform abnormalities in the IC, mostly on the side ipsilateral to run direction, and enhanced rhythmic 8-9Hz activity in the cortex. With repetition of the subcortical seizures and kindling development, a secondary cortical discharge began to follow the IC seizure. The secondary discharge initially involved the cortex homolateral to the side of dominant subcortical epileptiform abnormalities and behaviorally expressed as limbic (partial) clonus. Kindling progression was associated with bilateralization of the secondary cortical discharge, an increase in its amplitude and duration, intensification of associated behavioral seizures (from partial clonus to generalized tonic-clonic convulsions). Thus, ictal recordings during brief audiogenic running seizures showed their focal

  12. Two cases with megalencephalic leukoencephalopathy with subcortical cysts and MLC1 mutations in the Turkish population.

    PubMed

    Yiş, Uluç; Scheper, Gert C; Uran, Nedret; Unalp, Aycan; Cakmakçi, Handan; Hiz-Kurul, Semra; Dirik, Eray; van der Knaap, Marjo S

    2010-01-01

    Megalencephalic leukoencephalopathy with subcortical cysts is a rare leukodystrophy that is characterized by macrocephaly and a slowly progressive clinical course. It is one of the most commonly reported leukoencephalopathies in Turkey. Mutations in the MLC1 gene are the main cause of the disease. We report two patients with megalencephalic leukoencephalopathy with subcortical cysts with confirmed mutations in the MLC1 gene. The mutation in the second patient was novel. We also review identified mutations in the Turkish population.

  13. Comparative Study of Subcortical Atrophy in Patients with Frontotemporal Dementia and Dementia with Extrapyramidal Signs

    PubMed Central

    Caixeta, Leonardo; Vieira, Renata Teles; Paes, Flávia; Carta, Mauro Giovanni; Nardi, Antonio Egidio; Arias-Carrión, Oscar; Rocha, Nuno B. F; Budde, Henning; Machado, Sergio

    2015-01-01

    Objectives : To investigate the severity of subcortical atrophy in frontotemporal dementia (FTD) without extrapyramidal symptoms (EPS) and dementia with EPS. In addition, we aim to verify if there is correlation between demographic and clinical characteristics and subcortical atrophy in the groups. Methodology : The sample was composed of 21 patients with dementia and EPS as well as 19 patients with FTD without EPS. A linear assessment was conducted in order to identify the degree of subcortical atrophy (i.e., bifrontal index - BFI) using MRI. Moreover, the Mini-Mental State Examination (MMSE), Pfeffer Functional Activities Questionnaire (FAQ) and the Clinical Dementia Rating (CDR) were used to investigate clinical aspects. Results : It was verified that patients with dementia and EPS was older than the patients with FTD (p=0.01). The severity of cognitive deficits was associated with BFI, as well as the dementia severity in the EPS group. Conclusion : FTD group presented mean BFI scores above the cutoff for normal elderly population, indicating the presence of subcortical atrophy in this group. Mean BFI was higher (although not statistically significant) in FTD group than in dementia with EPS, which can suggest at least that subcortical pathology in FTD may be as important as in the dementia with EPS group. Subcortical atrophy is a good biological marker for cognitive deterioration in FTD and in dementia with EPS. PMID:25870648

  14. Cerebral, subcortical, and cerebellar activation evoked by selective stimulation of muscle and cutaneous afferents: an fMRI study.

    PubMed

    Wardman, Daniel L; Gandevia, Simon C; Colebatch, James G

    2014-01-01

    Abstract We compared the brain areas that showed significant flow changes induced by selective stimulation of muscle and cutaneous afferents using fMRI BOLD imaging. Afferents arising from the right hand were studied in eight volunteers with electrical stimulation of the digital nerve of the index finger and over the motor point of the FDI muscle. Both methods evoked areas of significant activation cortically, subcortically, and in the cerebellum. Selective muscle afferent stimulation caused significant activation in motor-related areas. It also caused significantly greater activation within the contralateral precentral gyrus, insula, and within the ipsilateral cerebellum as well as greater areas of reduced blood flow when compared to the cutaneous stimuli. We demonstrated separate precentral and postcentral foci of excitation with muscle afferent stimulation. We conclude, contrary to the findings with evoked potentials, that muscle afferents evoke more widespread cortical, subcortical, and cerebellar activation than do cutaneous afferents. This emphasizes the importance, for studies of movement, of matching the kinematic aspects in order to avoid the results being confounded by alterations in muscle afferent activation. The findings are consistent with clinical observations of the movement consequences of sensory loss and may also be the basis for the contribution of disturbed sensorimotor processing to disorders of movement.

  15. Cerebral, subcortical, and cerebellar activation evoked by selective stimulation of muscle and cutaneous afferents: an fMRI study

    PubMed Central

    Wardman, Daniel L.; Gandevia, Simon C.; Colebatch, James G.

    2014-01-01

    Abstract We compared the brain areas that showed significant flow changes induced by selective stimulation of muscle and cutaneous afferents using fMRI BOLD imaging. Afferents arising from the right hand were studied in eight volunteers with electrical stimulation of the digital nerve of the index finger and over the motor point of the FDI muscle. Both methods evoked areas of significant activation cortically, subcortically, and in the cerebellum. Selective muscle afferent stimulation caused significant activation in motor‐related areas. It also caused significantly greater activation within the contralateral precentral gyrus, insula, and within the ipsilateral cerebellum as well as greater areas of reduced blood flow when compared to the cutaneous stimuli. We demonstrated separate precentral and postcentral foci of excitation with muscle afferent stimulation. We conclude, contrary to the findings with evoked potentials, that muscle afferents evoke more widespread cortical, subcortical, and cerebellar activation than do cutaneous afferents. This emphasizes the importance, for studies of movement, of matching the kinematic aspects in order to avoid the results being confounded by alterations in muscle afferent activation. The findings are consistent with clinical observations of the movement consequences of sensory loss and may also be the basis for the contribution of disturbed sensorimotor processing to disorders of movement. PMID:24771687

  16. Subcortical Plasticity Following Perceptual Learning in a Pitch Discrimination Task

    PubMed Central

    Plack, Christopher J.

    2010-01-01

    Practice can lead to dramatic improvements in the discrimination of auditory stimuli. In this study, we investigated changes of the frequency-following response (FFR), a subcortical component of the auditory evoked potentials, after a period of pitch discrimination training. Twenty-seven adult listeners were trained for 10 h on a pitch discrimination task using one of three different complex tone stimuli. One had a static pitch contour, one had a rising pitch contour, and one had a falling pitch contour. Behavioral measures of pitch discrimination and FFRs for all the stimuli were measured before and after the training phase for these participants, as well as for an untrained control group (n = 12). Trained participants showed significant improvements in pitch discrimination compared to the control group for all three trained stimuli. These improvements were partly specific for stimuli with the same pitch modulation (dynamic vs. static) and with the same pitch trajectory (rising vs. falling) as the trained stimulus. Also, the robustness of FFR neural phase locking to the sound envelope increased significantly more in trained participants compared to the control group for the static and rising contour, but not for the falling contour. Changes in FFR strength were partly specific for stimuli with the same pitch modulation (dynamic vs. static) of the trained stimulus. Changes in FFR strength, however, were not specific for stimuli with the same pitch trajectory (rising vs. falling) as the trained stimulus. These findings indicate that even relatively low-level processes in the mature auditory system are subject to experience-related change. PMID:20878201

  17. Bilateral subcortical heterotopia with partial callosal agenesis in a mouse mutant.

    PubMed

    Rosen, G D; Azoulay, N G; Griffin, E G; Newbury, A; Koganti, L; Fujisaki, N; Takahashi, E; Grant, P E; Truong, D T; Fitch, R H; Lu, L; Williams, R W

    2013-04-01

    Cognition and behavior depend on the precise placement and interconnection of complex ensembles of neurons in cerebral cortex. Mutations that disrupt migration of immature neurons from the ventricular zone to the cortical plate have provided major insight into mechanisms of brain development and disease. We have discovered a new and highly penetrant spontaneous mutation that leads to large nodular bilateral subcortical heterotopias with partial callosal agenesis. The mutant phenotype was first detected in a colony of fully inbred BXD29 mice already known to harbor a mutation in Tlr4. Neurons confined to the heterotopias are mainly born in midgestation to late gestation and would normally have migrated into layers 2-4 of overlying neocortex. Callosal cross-sectional area and fiber number are reduced up to 50% compared with coisogenic wildtype BXD29 substrain controls. Mutants have a pronounced and highly selective defect in rapid auditory processing. The segregation pattern of the mutant phenotype is most consistent with a two-locus autosomal recessive model, and selective genotyping definitively rules out the Tlr4 mutation as a cause. The discovery of a novel mutation with strong pleiotropic anatomical and behavioral effects provides an important new resource for dissecting molecular mechanisms and functional consequences of errors of neuronal migration.

  18. Top-Down-Mediated Facilitation in the Visual Cortex Is Gated by Subcortical Neuromodulation.

    PubMed

    Pafundo, Diego E; Nicholas, Mark A; Zhang, Ruilin; Kuhlman, Sandra J

    2016-03-09

    Response properties in primary sensory cortices are highly dependent on behavioral state. For example, the nucleus basalis of the forebrain plays a critical role in enhancing response properties of excitatory neurons in primary visual cortex (V1) during active exploration and learning. Given the strong reciprocal connections between hierarchically arranged cortical regions, how are increases in sensory response gain constrained to prevent runaway excitation? To explore this, we used in vivo two-photon guided cell-attached recording in conjunction with spatially restricted optogenetic photo-inhibition of higher-order visual cortex in mice. We found that the principle feedback projection to V1 originating from the lateral medial area (LM) facilitated visual responses in layer 2/3 excitatory neurons by ∼20%. This facilitation was reduced by half during basal forebrain activation due to differential response properties between LM and V1. Our results demonstrate that basal-forebrain-mediated increases in response gain are localized to V1 and are not propagated to LM and establish that subcortical modulation of visual cortex is regionally distinct.

  19. Changes of Brain Connectivity in the Primary Motor Cortex After Subcortical Stroke

    PubMed Central

    Li, Yongxin; Wang, Defeng; Zhang, Heye; Wang, Ya; Wu, Ping; Zhang, Hongwu; Yang, Yang; Huang, Wenhua

    2016-01-01

    Abstract The authors investigated the changes in connectivity networks of the bilateral primary motor cortex (M1) of subcortical stroke patients using a multimodal neuroimaging approach with antiplatelet therapy. Nineteen patients were scanned at 2 time points: before and 1 month after the treatment. The authors assessed the resting-state functional connectivity (FC) and probabilistic fiber tracking of left and right M1 of every patient, and then compared these results to the 15 healthy controls. The authors also evaluated the correlations between the neuroimaging results and clinical scores. Compared with the controls, the patients showed a significant decrease of FC in the contralateral motor cortex before treatment, and the disrupted FC was restored after treatment. The fiber tracking results in the controls indicated that the body of the corpus callosum should be the main pathway connecting the M1 and contralateral hemispheres. All patients exhibited reduced probability of structural connectivity within this pathway before treatment and which was restored after treatment. Significant correlations were also found in these patients between the connectivity results and clinical scores, which might imply that the connectivity of M1 can be used to evaluate the motor skills in stroke patients. These findings can help elucidate the neural mechanisms responsible for the brain connectivity recovery after stroke. PMID:26871777

  20. Cortical and subcortical gamma amino acid butyric acid deficits in anxiety and stress disorders: Clinical implications

    PubMed Central

    Goddard, Andrew W

    2016-01-01

    Anxiety and stress disorders are a major public health issue. However, their pathophysiology is still unclear. The gamma amino acid butyric acid (GABA) neurochemical system has been strongly implicated in their pathogenesis and treatment by numerous preclinical and clinical studies, the most recent of which have been highlighted and critical review in this paper. Changes in cortical GABA appear related to normal personality styles and responses to stress. While there is accumulating animal and human neuroimaging evidence of cortical and subcortical GABA deficits across a number of anxiety conditions, a clear pattern of findings in specific brain regions for a given disorder is yet to emerge. Neuropsychiatric conditions with anxiety as a clinical feature may have GABA deficits as an underlying feature. Different classes of anxiolytic therapies support GABA function, and this may be an area in which newer GABA neuroimaging techniques could soon offer more personalized therapy. Novel GABAergic pharmacotherapies in development offer potential improvements over current therapies in reducing sedative and physiologic dependency effects, while offering rapid anxiolysis. PMID:27014597

  1. Distinct structural neural patterns of trait physical and social anhedonia: evidence from cortical thickness, subcortical volumes and inter-regional correlations.

    PubMed

    Wang, Yi; Deng, Yi; Fung, Germaine; Liu, Wen-hua; Wei, Xin-hua; Jiang, Xin-qing; Lui, Simon S Y; Cheung, Eric F C; Chan, Raymond C K

    2014-12-30

    Anhedonia is an enduring trait accounting for the reduced capacity to experience pleasure. Few studies have investigated the brain structural features associated with trait anhedonia. In this study, the relationships between cortical thickness, volume of subcortical structures and scores on the Chapman physical and social anhedonia scales were examined in a non-clinical sample (n=72, 35 males). FreeSurfer was used to examine the cortical thickness and the volume of six identified subcortical structures related to trait anhedonia. We found that the cortical thickness of the superior frontal gyrus and the volume of the pallidum in the left hemisphere were correlated with anhedonia scores in both physical and social aspects. Specifically, positive correlations were found between levels of social anhedonia and the thickness of the postcentral and the inferior parietal gyri. Cortico-subcortical inter-correlations between these clusters were also observed. Our findings revealed distinct correlation patterns of neural substrates with trait physical and social anhedonia in a non-clinical sample. These findings contribute to the understanding of the pathologies underlying the anhedonia phenotype in schizophrenia and other psychiatric disorders.

  2. Fractional anisotropy shows differential reduction in frontal-subcortical fiber bundles—A longitudinal MRI study of 76 middle-aged and older adults

    PubMed Central

    Vik, Alexandra; Hodneland, Erlend; Haász, Judit; Ystad, Martin; Lundervold, Astri J.; Lundervold, Arvid

    2015-01-01

    Motivated by the frontal- and white matter (WM) retrogenesis hypotheses and the assumptions that fronto-striatal circuits are especially vulnerable in normal aging, the goal of the present study was to identify fiber bundles connecting subcortical nuclei and frontal areas and obtain site-specific information about age related fractional anisotropy (FA) changes. Multimodal magnetic resonance image acquisitions [3D T1-weighted and diffusion weighted imaging (DWI)] were obtained from healthy older adults (N = 76, range 49–80 years at inclusion) at two time points, 3 years apart. A subset of the participants (N = 24) was included at a third time-point. In addition to the frontal-subcortical fibers, the anterior callosal fiber (ACF) and the corticospinal tract (CST) was investigated by its mean FA together with tract parameterization analysis. Our results demonstrated fronto-striatal structural connectivity decline (reduced FA) in normal aging with substantial inter-individual differences. The tract parameterization analysis showed that the along tract FA profiles were characterized by piece-wise differential changes along their extension rather than being uniformly affected. To the best of our knowledge, this is the first longitudinal study detecting age-related changes in frontal-subcortical WM connections in normal aging. PMID:26029102

  3. An Allometric Analysis of Sex and Sex Chromosome Dosage Effects on Subcortical Anatomy in Humans

    PubMed Central

    Clasen, Liv; Giedd, Jay N.; Blumenthal, Jonathan; Lerch, Jason P.; Chakravarty, M. Mallar; Raznahan, Armin

    2016-01-01

    Structural neuroimaging of humans with typical and atypical sex-chromosome complements has established the marked influence of both Yand X-/Y-chromosome dosage on total brain volume (TBV) and identified potential cortical substrates for the psychiatric phenotypes associated with sex-chromosome aneuploidy (SCA). Here, in a cohort of 354 humans with varying karyotypes (XX, XY, XXX, XXY, XYY, XXYY, XXXXY), we investigate sex and SCA effects on subcortical size and shape; focusing on the striatum, pallidum and thalamus. We find large effect-size differences in the volume and shape of all three structures as a function of sex and SCA. We correct for TBV effects with a novel allometric method harnessing normative scaling rules for subcortical size and shape in humans, which we derive here for the first time. We show that all three subcortical volumes scale sublinearly with TBV among healthy humans, mirroring known relationships between subcortical volume and TBV among species. Traditional TBV correction methods assume linear scaling and can therefore invert or exaggerate sex and SCA effects on subcortical anatomy. Allometric analysis restricts sex-differences to: (1) greater pallidal volume (PV) in males, and (2) relative caudate head expansion and ventral striatum contraction in females. Allometric analysis of SCA reveals that supernumerary X- and Y-chromosomes both cause disproportionate reductions in PV, and coordinated deformations of striatopallidal shape. Our study provides a novel understanding of sex and sex-chromosome dosage effects on subcortical organization, using an allometric approach that can be generalized to other basic and clinical structural neuroimaging settings. SIGNIFICANCE STATEMENT Sex and sex-chromosome dosage (SCD) are known to modulate human brain size and cortical anatomy, but very little is known regarding their impact on subcortical structures that work with the cortex to subserve a range of behaviors in health and disease. Moreover

  4. Decreased Activation of Subcortical Brain Areas in the Motor Fatigue State: An fMRI Study

    PubMed Central

    Hou, Li J.; Song, Zheng; Pan, Zhu J.; Cheng, Jia L.; Yu, Yong; Wang, Jun

    2016-01-01

    One aspect of motor fatigue is the exercise-induced reduction of neural activity to voluntarily drive the muscle or muscle group. Functional magnetic resonance imaging provides access to investigate the neural activation on the whole brain level and studies observed changes of activation intensity after exercise-induced motor fatigue in the sensorimotor cortex. However, in human, little evidence exists to demonstrate the role of subcortical brain regions in motor fatigue, which is contradict to abundant researches in rodent indicating that during simple movement, the activity of the basal ganglia is modulated by the state of motor fatigue. Thus, in present study, we explored the effect of motor fatigue on subcortical areas in human. A series of fMRI data were collected from 11 healthy subjects while they were executing simple motor tasks in two conditions: before and under the motor fatigue state. The results showed that in both conditions, movements evoked activation volumes in the sensorimotor areas, SMA, cerebellum, thalamus, and basal ganglia. Of primary importance are the results that the intensity and size of activation volumes in the subcortical areas (i.e., thalamus and basal ganglia areas) are significantly decreased during the motor fatigue state, implying that motor fatigue disturbs the motor control processing in a way that both sensorimotor areas and subcortical brain areas are less active. Further study is needed to clarify how subcortical areas contribute to the overall decreased activity of CNS during motor fatigue state. PMID:27536264

  5. Subcortical volumes differentiate Major Depressive Disorder, Bipolar Disorder, and remitted Major Depressive Disorder.

    PubMed

    Sacchet, Matthew D; Livermore, Emily E; Iglesias, Juan Eugenio; Glover, Gary H; Gotlib, Ian H

    2015-09-01

    Subcortical gray matter regions have been implicated in mood disorders, including Major Depressive Disorder (MDD) and Bipolar Disorder (BD). It is unclear, however, whether or how these regions differ among mood disorders and whether such abnormalities are state- or trait-like. In this study, we examined differences in subcortical gray matter volumes among euthymic BD, MDD, remitted MDD (RMD), and healthy (CTL) individuals. Using automated gray matter segmentation of T1-weighted MRI images, we estimated volumes of 16 major subcortical gray matter structures in 40 BD, 57 MDD, 35 RMD, and 61 CTL individuals. We used multivariate analysis of variance to examine group differences in these structures, and support vector machines (SVMs) to assess individual-by-individual classification. Analyses yielded significant group differences for caudate (p = 0.029) and ventral diencephalon (VD) volumes (p = 0.003). For the caudate, both the BD (p = 0.004) and the MDD (p = 0.037) participants had smaller volumes than did the CTL participants. For the VD, the MDD participants had larger volumes than did the BD and CTL participants (ps < 0.005). SVM distinguished MDD from BD with 59.5% accuracy. These findings indicate that mood disorders are characterized by anomalies in subcortical gray matter volumes and that the caudate and VD contribute uniquely to differential affective pathology. Identifying abnormalities in subcortical gray matter may prove useful for the prevention, diagnosis, and treatment of mood disorders.

  6. Subanaesthetic Ketamine Treatment Alters Prefrontal Cortex Connectivity With Thalamus and Ascending Subcortical Systems

    PubMed Central

    Dawson, Neil; Morris, Brian J.; Pratt, Judith A.

    2013-01-01

    Background: Acute treatment with subanaesthetic doses of NMDA receptor antagonists, such as ketamine, provides a translational model with relevance to many of the symptoms of schizophrenia. Previous studies have focused specifically on the prefrontal cortex (PFC) because this region is implicated in many of the functional deficits associated with this disorder and shows reduced activity (hypofrontality) in schizophrenia patients. Chronic NMDA antagonist treatment in rodents can also induce hypofrontality, although paradoxically acute NMDA receptor antagonist administration induces metabolic hyperfrontality. Methods: In this study, we use 2-deoxyglucose imaging data in mice to characterize acute ketamine-induced alterations in regional functional connectivity, a deeper analysis of the consequences of acute NMDA receptor hypofunction. Results: We show that acute ketamine treatment increases PFC metabolic activity while reducing metabolic activity in the dorsal reticular thalamic nucleus (dRT). This is associated with abnormal functional connectivity between the PFC and multiple thalamic nuclei, including the dRT, mediodorsal (MDthal), and anteroventral (AVthal) thalamus. In addition, we show that acute NMDA receptor blockade alters the functional connectivity of the serotonergic (dorsal raphe [DR]), noradrenergic (locus coeruleus [LC]), and cholinergic (vertical limb of the diagonal band of broca [VDB]) systems. Conclusions: Together with other emerging data, these findings suggest that the reticular nucleus of the thalamus, along with the diffusely projecting subcortical aminergic/cholinergic systems, represent a primary site of action for ketamine in reproducing the diverse symptoms of schizophrenia. Our results also demonstrate the added scientific insight gained by characterizing the functional connectivity of discrete brain regions from brain imaging data gained in a preclinical context. PMID:22114100

  7. Listening to the brainstem: musicianship enhances intelligibility of subcortical representations for speech.

    PubMed

    Weiss, Michael W; Bidelman, Gavin M

    2015-01-28

    Auditory experiences including musicianship and bilingualism have been shown to enhance subcortical speech encoding operating below conscious awareness. Yet, the behavioral consequence of such enhanced subcortical auditory processing remains undetermined. Exploiting their remarkable fidelity, we examined the intelligibility of auditory playbacks (i.e., "sonifications") of brainstem potentials recorded in human listeners. We found naive listeners' behavioral classification of sonifications was faster and more categorical when evaluating brain responses recorded in individuals with extensive musical training versus those recorded in nonmusicians. These results reveal stronger behaviorally relevant speech cues in musicians' neural representations and demonstrate causal evidence that superior subcortical processing creates a more comprehensible speech signal (i.e., to naive listeners). We infer that neural sonifications of speech-evoked brainstem responses could be used in the early detection of speech-language impairments due to neurodegenerative disorders, or in objectively measuring individual differences in speech reception solely by listening to individuals' brain activity.

  8. A Case of Generalized Auditory Agnosia with Unilateral Subcortical Brain Lesion

    PubMed Central

    Suh, Hyee; Kim, Soo Yeon; Kim, Sook Hee; Chang, Jae Hyeok; Shin, Yong Beom; Ko, Hyun-Yoon

    2012-01-01

    The mechanisms and functional anatomy underlying the early stages of speech perception are still not well understood. Auditory agnosia is a deficit of auditory object processing defined as a disability to recognize spoken languages and/or nonverbal environmental sounds and music despite adequate hearing while spontaneous speech, reading and writing are preserved. Usually, either the bilateral or unilateral temporal lobe, especially the transverse gyral lesions, are responsible for auditory agnosia. Subcortical lesions without cortical damage rarely causes auditory agnosia. We present a 73-year-old right-handed male with generalized auditory agnosia caused by a unilateral subcortical lesion. He was not able to repeat or dictate but to perform fluent and comprehensible speech. He could understand and read written words and phrases. His auditory brainstem evoked potential and audiometry were intact. This case suggested that the subcortical lesion involving unilateral acoustic radiation could cause generalized auditory agnosia. PMID:23342322

  9. A case of generalized auditory agnosia with unilateral subcortical brain lesion.

    PubMed

    Suh, Hyee; Shin, Yong-Il; Kim, Soo Yeon; Kim, Sook Hee; Chang, Jae Hyeok; Shin, Yong Beom; Ko, Hyun-Yoon

    2012-12-01

    The mechanisms and functional anatomy underlying the early stages of speech perception are still not well understood. Auditory agnosia is a deficit of auditory object processing defined as a disability to recognize spoken languages and/or nonverbal environmental sounds and music despite adequate hearing while spontaneous speech, reading and writing are preserved. Usually, either the bilateral or unilateral temporal lobe, especially the transverse gyral lesions, are responsible for auditory agnosia. Subcortical lesions without cortical damage rarely causes auditory agnosia. We present a 73-year-old right-handed male with generalized auditory agnosia caused by a unilateral subcortical lesion. He was not able to repeat or dictate but to perform fluent and comprehensible speech. He could understand and read written words and phrases. His auditory brainstem evoked potential and audiometry were intact. This case suggested that the subcortical lesion involving unilateral acoustic radiation could cause generalized auditory agnosia.

  10. An Allometric Analysis of Sex and Sex Chromosome Dosage Effects on Subcortical Anatomy in Humans.

    PubMed

    Reardon, Paul Kirkpatrick; Clasen, Liv; Giedd, Jay N; Blumenthal, Jonathan; Lerch, Jason P; Chakravarty, M Mallar; Raznahan, Armin

    2016-02-24

    Structural neuroimaging of humans with typical and atypical sex-chromosome complements has established the marked influence of both Yand X-/Y-chromosome dosage on total brain volume (TBV) and identified potential cortical substrates for the psychiatric phenotypes associated with sex-chromosome aneuploidy (SCA). Here, in a cohort of 354 humans with varying karyotypes (XX, XY, XXX, XXY, XYY, XXYY, XXXXY), we investigate sex and SCA effects on subcortical size and shape; focusing on the striatum, pallidum and thalamus. We find large effect-size differences in the volume and shape of all three structures as a function of sex and SCA. We correct for TBV effects with a novel allometric method harnessing normative scaling rules for subcortical size and shape in humans, which we derive here for the first time. We show that all three subcortical volumes scale sublinearly with TBV among healthy humans, mirroring known relationships between subcortical volume and TBV among species. Traditional TBV correction methods assume linear scaling and can therefore invert or exaggerate sex and SCA effects on subcortical anatomy. Allometric analysis restricts sex-differences to: (1) greater pallidal volume (PV) in males, and (2) relative caudate head expansion and ventral striatum contraction in females. Allometric analysis of SCA reveals that supernumerary X- and Y-chromosomes both cause disproportionate reductions in PV, and coordinated deformations of striatopallidal shape. Our study provides a novel understanding of sex and sex-chromosome dosage effects on subcortical organization, using an allometric approach that can be generalized to other basic and clinical structural neuroimaging settings.

  11. A Rapid Subcortical Amygdala Route for Faces Irrespective of Spatial Frequency and Emotion.

    PubMed

    McFadyen, Jessica; Mermillod, Martial; Mattingley, Jason B; Halász, Veronika; Garrido, Marta I

    2017-03-10

    There is significant controversy over the existence and function of a direct subcortical visual pathway to the amygdala. It is thought that this pathway rapidly transmits low spatial frequency information to the amygdala independently of the cortex and yet the directionality of this function has never been determined. We used magnetoencephalography to measure neural activity while human participants discriminated the gender of neutral and fearful faces filtered for low or high spatial frequencies. We applied dynamic causal modelling to demonstrate that the most likely underlying neural network consisted of a pulvinar-amygdala connection that was uninfluenced by spatial frequency or emotion, and a cortical-amygdala connection that conveyed high spatial frequencies. Crucially, data-driven neural simulations revealed a clear temporal advantage of the subcortical connection over the cortical connection in influencing amygdala activity. Thus, our findings support the existence of a rapid subcortical pathway that is non-selective in terms of the spatial frequency or emotional content of faces. We propose that that the 'coarseness' of the subcortical route may be better reframed as 'generalised'.SIGNIFICANCE STATEMENTThe human amygdala co-ordinates how we respond to biologically relevant stimuli, such as threat or reward. It has been postulated that the amygdala first receives visual input via a rapid subcortical route that conveys 'coarse' information, namely low spatial frequencies. For the first time, the present paper provides direction-specific evidence from computational modelling that the subcortical route plays a generalised role in visual processing by rapidly transmitting raw, unfiltered information directly to the amygdala. This calls into question a widely held assumption across human and animal research that fear responses are produced faster by low spatial frequencies. Our proposed mechanism suggests organisms quickly generate fear responses to a wide range

  12. Essential Subcortical Tracts in Language and Reading. 3D-Tractography for Clinical Practice and Anatomic Correlation with Intraoperative Subcortical Electrostimulation.

    PubMed

    Jiménez-Peña, M M; Gil-Robles, S; Cano-Alonso, R; Recio-Rodríguez, M; Carrascoso-Arranz, J; Ruiz-Ocaña, C; Martínez-Vega, V

    2017-03-01

    Diffusion tensor imaging (DTI) and tractography provide the neurosurgeon with a valid 3D view of the white matter tracts of the brain for the presurgical planning of the treatment of lesions close to eloquent areas, this being one of the principal clinical applications of this technique. In this article, we describe through practical cases the anatomic relationships of white matter tracts that are essential for language and reading, based on DTI studies and the excellent anatomic correlation with the intraoperative subcortical map.

  13. Effects of subcortical cerebrovascular lesions on cortical hemodynamic parameters assessed by perfusion magnetic resonance imaging.

    PubMed

    Nighoghossian, N; Berthezene, Y; Adeleine, P; Wiart, M; Damien, J; Derex, L; Itti, R; Froment, J C; Trouillas, P

    1999-01-01

    A simultaneous decrease of cerebral blood volume (CBV) and cerebral blood flow (CBF) has been described after subcortical stroke with positron emission tomography. However, this imaging modality cannot be applied routinely to stroke patients. Dynamic susceptibility contrast-enhanced MRI techniques (DSC-MRI) might be interesting in the assessment of these effects. Dynamic T2-weighted echo planar imaging was used to produce DSC-MR images during an intravenous bolus injection of gadopentetate dimeglumine in 9 patients who experienced a subcortical stroke involving thalamus or basal ganglia and in 8 control subjects. A series of 50 consecutive images at 1-second intervals was acquired at the anatomic level of the centrum semiovale quite distant from the subcortical lesion, rCBF and rCBV were determined over frontal and parietal regions of interest and through the entire cortical mantle. DSC-MRI enabled the detection of hemodynamic changes induced by subcortical stroke. Analysis of rCBV and rCBF values showed that the hemodynamic parameters were significantly decreased on the affected side. In controls mean rCBF and rCBV values recorded over the whole cortical mantle of each hemisphere showed no significant interhemispheric asymmetry.

  14. Formulaic Language in Parkinson's Disease and Alzheimer's Disease: Complementary Effects of Subcortical and Cortical Dysfunction

    ERIC Educational Resources Information Center

    Van Lancker Sidtis, Diana; Choi, JiHee; Alken, Amy; Sidtis, John J.

    2015-01-01

    Purpose: The production of formulaic expressions (conversational speech formulas, pause fillers, idioms, and other fixed expressions) is excessive in the left hemisphere and deficient in the right hemisphere and in subcortical stroke. Speakers with Alzheimer's disease (AD), having functional basal ganglia, reveal abnormally high proportions of…

  15. Patients with extratemporal lobe epilepsy do not differ from healthy subjects with respect to subcortical volumes

    PubMed Central

    Gartner, B; Seeck, M; Michel, C; Delavelle, J; Lazeyras, F

    2004-01-01

    Background: Evidence from previous volumetric magnetic resonance studies has revealed that patients with chronic temporal lobe epilepsy show atrophy of distinct subcortical nuclei, predominantly ipsilateral to the focus side. We were interested to find out if there is also selective subcortical atrophy in patients suffering from long standing extratemporal lobe epilepsy. Methods: Thirty one patients in whom pre-surgical evaluation unambiguously localised an extratemporal focus were included in this study. Using high resolution magnetic resonance imaging, the volumes of the caudate nuclei, putamen, pallidum, and thalamus were measured bilaterally in both hemispheres and compared with measurements obtained in 15 healthy volunteers. Results: No significant difference in volumes was found between the two subject groups, or in any subgroup of extratemporal lobe epilepsy patients, nor was there any relation to clinical variables such as age of onset, overall seizure frequency, or disease duration. However, patients who had no or only rare generalised tonic–clonic seizures seemed to differ from the other patients and controls in that they had smaller putamen volumes bilaterally (p<0.001). Conclusion: We concluded that extratemporal lobe epilepsy in general is not associated with diminished volumes in the studied subcortical structures, which contrasts with findings in temporal lobe epilepsy patients. Thus, both entities differ both cortically and subcortically. However, we found that small putamen volume was bilaterally associated with absent or rare generalised tonic–clonic seizures, implicating the putamen in the control of the most disabling seizure type, independent of the site of neocortical focus. PMID:15026503

  16. A Comparison of Picture Description Abilities in Individuals with Vascular Subcortical Lesions and Huntington's Disease

    ERIC Educational Resources Information Center

    Jensen, Angela M.; Chenery, Helen J.; Copland, David A.

    2006-01-01

    The lexical-semantic and syntactic abilities of a group of individuals with chronic nonthalamic subcortical (NS) lesions following stroke (n=6) were investigated using the Western Aphasia Battery (WAB) picture description task [Kertesz, A. (1982). "The Western aphasia battery." New York: Grune and Stratton] and compared with those of a…

  17. Subcortical Preprocessing of Oral Language: A Holistic Model for Language Cognition.

    ERIC Educational Resources Information Center

    George, Don

    This paper considers the process by which humans are able to select from the complex string of sounds impinging on the ear and understand certain frequency combinations to be linguistic signals while other combinations are not. A brief review of the complex subcortical region, particularly the known but seldom studied reticular system, indicates…

  18. Double inversion recovery magnetic resonance imaging of subcortical band heterotopia: a report of 2 cases.

    PubMed

    Zhang, Quan; Zhang, Yunting; Zhang, Jing; Li, Qiong

    2011-01-01

    We report 2 cases of subcortical band heterotopia (SBH) with emphasis on double inversion recovery (DIR) magnetic resonance imaging (MRI). The heterotopic gray matter demonstrated homogeneous high signal intensity and the delineation between the SBH and white matter was distinctly depicted on DIR MRI. Double inversion recovery is a useful adjunct to conventional MRI for the diagnosis of SBH.

  19. FANCD2 re-expression is associated with glioma grade and chemical inhibition of the Fanconi Anaemia pathway sensitises gliomas to chemotherapeutic agents.

    PubMed

    Patil, Abhijit A; Sayal, Parag; Depondt, Marie-Lise; Beveridge, Ryan D; Roylance, Anthony; Kriplani, Deepti H; Myers, Katie N; Cox, Angela; Jellinek, David; Fernando, Malee; Carroll, Thomas A; Collis, Spencer J

    2014-08-15

    Brain tumours kill more children and adults under 40 than any other cancer. Around half of primary brain tumours are glioblastoma multiforme (GBMs) where treatment remains a significant challenge, where survival rates have improved little over the last 40 years, thus highlighting an unmet need for the identification/development of novel therapeutic targets and agents to improve GBM treatment. Using archived and fresh glioma tissue, we show that in contrast to normal brain or benign schwannomas GBMs exhibit re-expression of FANCD2, a key protein of the Fanconi Anaemia (FA) DNA repair pathway, and possess an active FA pathway. Importantly, FANCD2 expression levels are strongly associated with tumour grade, revealing a potential exploitable therapeutic window to allow inhibition of the FA pathway in tumour cells, whilst sparing normal brain tissue. Using several small molecule inhibitors of the FA pathway in combination with isogenic FA-proficient/deficient glioma cell lines as well as primary GBM cultures, we demonstrate that inhibition of the FA pathway sensitises gliomas to the chemotherapeutic agents Temozolomide and Carmustine. Our findings therefore provide a strong rationale for the development of novel and potent inhibitors of the FA pathway to improve the treatment of GBMs, which may ultimately impact on patient outcome.

  20. FANCD2 re-expression is associated with glioma grade and chemical inhibition of the Fanconi Anaemia pathway sensitises gliomas to chemotherapeutic agents

    PubMed Central

    Patil, Abhijit A.; Sayal, Parag; Depondt, Marie-Lise; Beveridge, Ryan D.; Roylance, Anthony; Kriplani, Deepti H.; Myers, Katie N.; Cox, Angela; Jellinek, David; Fernando, Malee; Carroll, Thomas A.; Collis, Spencer J.

    2014-01-01

    Brain tumours kill more children and adults under 40 than any other cancer. Around half of primary brain tumours are glioblastoma multiforme (GBMs) where treatment remains a significant challenge. GBM survival rates have improved little over the last 40 years, thus highlighting an unmet need for the identification/development of novel therapeutic targets and agents to improve GBM treatment. Using archived and fresh glioma tissue, we show that in contrast to normal brain or benign schwannomas GBMs exhibit re-expression of FANCD2, a key protein of the Fanconi Anaemia (FA) DNA repair pathway, and possess an active FA pathway. Importantly, FANCD2 expression levels are strongly associated with tumour grade, revealing a potential exploitable therapeutic window to allow inhibition of the FA pathway in tumour cells, whilst sparing normal brain tissue. Using several small molecule inhibitors of the FA pathway in combination with isogenic FA-proficient/deficient glioma cell lines as well as primary GBM cultures, we demonstrate that inhibition of the FA pathway sensitises gliomas to the chemotherapeutic agents Temozolomide and Carmustine. Our findings therefore provide a strong rationale for the development of novel and potent inhibitors of the FA pathway to improve the treatment of GBMs, which may ultimately impact on patient outcome. PMID:25071006

  1. Patterns of Cortical and Subcortical Amyloid Burden across Stages of Preclinical Alzheimer’s Disease

    PubMed Central

    Edmonds, Emily C.; Bangen, Katherine J.; Delano-Wood, Lisa; Nation, Daniel A.; Furst, Ansgar J.; Salmon, David P.; Bondi, Mark W.

    2017-01-01

    Objectives We examined florbetapir positron emission tomography (PET) amyloid scans across stages of preclinical Alzheimer’s disease (AD) in cortical, allocortical, and subcortical regions. Stages were characterized using empirically defined methods. Methods A total of 312 cognitively normal Alzheimer’s Disease Neuroimaging Initiative participants completed a neuropsychological assessment and florbetapir PET scan. Participants were classified into stages of preclinical AD using (1) a novel approach based on the number of abnormal biomarkers/cognitive markers each individual possessed, and (2) National Institute on Aging and the Alzheimer’s Association (NIA-AA) criteria. Preclinical AD groups were compared to one another and to a mild cognitive impairment (MCI) sample on florbetapir standardized uptake value ratios (SUVRs) in cortical and allocortical/subcortical regions of interest (ROIs). Results Amyloid deposition increased across stages of preclinical AD in all cortical ROIs, with SUVRs in the later stages reaching levels seen in MCI. Several subcortical areas showed a pattern of results similar to the cortical regions; however, SUVRs in the hippocampus, pallidum, and thalamus largely did not differ across stages of preclinical AD. Conclusions Substantial amyloid accumulation in cortical areas has already occurred before one meets criteria for a clinical diagnosis. Potential explanations for the unexpected pattern of results in some allocortical/subcortical ROIs include lack of correspondence between (1) cerebrospinal fluid and florbetapir PET measures of amyloid, or between (2) subcortical florbetapir PET SUVRs and underlying neuropathology. Findings support the utility of our novel method for staging preclinical AD. By combining imaging biomarkers with detailed cognitive assessment to better characterize preclinical AD, we can advance our understanding of who is at risk for future progression. PMID:27903335

  2. New tissue priors for improved automated classification of subcortical brain structures on MRI☆

    PubMed Central

    Lorio, S.; Fresard, S.; Adaszewski, S.; Kherif, F.; Chowdhury, R.; Frackowiak, R.S.; Ashburner, J.; Helms, G.; Weiskopf, N.; Lutti, A.; Draganski, B.

    2016-01-01

    Despite the constant improvement of algorithms for automated brain tissue classification, the accurate delineation of subcortical structures using magnetic resonance images (MRI) data remains challenging. The main difficulties arise from the low gray-white matter contrast of iron rich areas in T1-weighted (T1w) MRI data and from the lack of adequate priors for basal ganglia and thalamus. The most recent attempts to obtain such priors were based on cohorts with limited size that included subjects in a narrow age range, failing to account for age-related gray-white matter contrast changes. Aiming to improve the anatomical plausibility of automated brain tissue classification from T1w data, we have created new tissue probability maps for subcortical gray matter regions. Supported by atlas-derived spatial information, raters manually labeled subcortical structures in a cohort of healthy subjects using magnetization transfer saturation and R2* MRI maps, which feature optimal gray-white matter contrast in these areas. After assessment of inter-rater variability, the new tissue priors were tested on T1w data within the framework of voxel-based morphometry. The automated detection of gray matter in subcortical areas with our new probability maps was more anatomically plausible compared to the one derived with currently available priors. We provide evidence that the improved delineation compensates age-related bias in the segmentation of iron rich subcortical regions. The new tissue priors, allowing robust detection of basal ganglia and thalamus, have the potential to enhance the sensitivity of voxel-based morphometry in both healthy and diseased brains. PMID:26854557

  3. The Relationship between Intelligence and Anxiety: An Association with Subcortical White Matter Metabolism

    PubMed Central

    Coplan, Jeremy D.; Hodulik, Sarah; Mathew, Sanjay J.; Mao, Xiangling; Hof, Patrick R.; Gorman, Jack M.; Shungu, Dikoma C.

    2012-01-01

    We have demonstrated in a previous study that a high degree of worry in patients with generalized anxiety disorder (GAD) correlates positively with intelligence and that a low degree of worry in healthy subjects correlates positively with intelligence. We have also shown that both worry and intelligence exhibit an inverse correlation with certain metabolites in the subcortical white matter. Here we re-examine the relationships among generalized anxiety, worry, intelligence, and subcortical white matter metabolism in an extended sample. Results from the original study were combined with results from a second study to create a sample comprised of 26 patients with GAD and 18 healthy volunteers. Subjects were evaluated using the Penn State Worry Questionnaire, the Wechsler Brief intelligence quotient (IQ) assessment, and proton magnetic resonance spectroscopic imaging (1H-MRSI) to measure subcortical white matter metabolism of choline and related compounds (CHO). Patients with GAD exhibited higher IQ’s and lower metabolite concentrations of CHO in the subcortical white matter in comparison to healthy volunteers. When data from GAD patients and healthy controls were combined, relatively low CHO predicted both relatively higher IQ and worry scores. Relatively high anxiety in patients with GAD predicted high IQ whereas relatively low anxiety in controls also predicted high IQ. That is, the relationship between anxiety and intelligence was positive in GAD patients but inverse in healthy volunteers. The collective data suggest that both worry and intelligence are characterized by depletion of metabolic substrate in the subcortical white matter and that intelligence may have co-evolved with worry in humans. PMID:22347183

  4. Asymmetries of Dark and Bright Negative Afterimages Are Paralleled by Subcortical ON and OFF Poststimulus Responses.

    PubMed

    Li, Hui; Liu, Xu; Andolina, Ian M; Li, Xiaohong; Lu, Yiliang; Spillmann, Lothar; Wang, Wei

    2017-02-22

    Humans are more sensitive to luminance decrements than increments, as evidenced by lower thresholds and shorter latencies for dark stimuli. This asymmetry is consistent with results of neurophysiological recordings in dorsal lateral geniculate nucleus (dLGN) and primary visual cortex (V1) of cat and monkey. Specifically, V1 population responses demonstrate that darks elicit higher levels of activation than brights, and the latency of OFF responses in dLGN and V1 is shorter than that of ON responses. The removal of a dark or bright disc often generates the perception of a negative afterimage, and here we ask whether there also exist asymmetries for negative afterimages elicited by dark and bright discs. If so, do the poststimulus responses of subcortical ON and OFF cells parallel such afterimage asymmetries? To test these hypotheses, we performed psychophysical experiments in humans and single-cell/S-potential recordings in cat dLGN. Psychophysically, we found that bright afterimages elicited by luminance decrements are stronger and last longer than dark afterimages elicited by luminance increments of equal sizes. Neurophysiologically, we found that ON cells responded to the removal of a dark disc with higher firing rates that were maintained for longer than OFF cells to the removal of a bright disc. The ON and OFF cell asymmetry was most pronounced at long stimulus durations in the dLGN. We conclude that subcortical response strength differences between ON and OFF channels parallel the asymmetries between bright and dark negative afterimages, further supporting a subcortical origin of bright and dark afterimage perception.SIGNIFICANCE STATEMENT Afterimages are physiological aftereffects following stimulation of the eye, the study of which helps us to understand how our visual brain generates visual perception in the absence of physical stimuli. We report, for the first time to our knowledge, asymmetries between bright and dark negative afterimages elicited by

  5. Subcortical and Cortical Structural Central Nervous System Changes and Attention Processing Deficits in Preschool-Aged Children with Prenatal Methamphetamine and Tobacco Exposure

    PubMed Central

    Derauf, Chris; Lester, Barry M.; Neyzi, Nurunisa; Kekatpure, Minal; Gracia, Luis; Davis, James; Kallianpur, Kalpana; Efird, Jimmy T.; Kosofsky, Barry

    2014-01-01

    Objective To examine the independent contributions of prenatal methamphetamine exposure (PME) and prenatal tobacco exposure (PTE) on brain morphology among a sample of nonalcohol-exposed 3- to 5-year-old children followed prospectively since birth. Study Design The sample included 20 children with PME (19 with PTE) and 15 comparison children (7 with PTE), matched on race, birth weight, maternal education and type of insurance. Subcortical and cortical volumes and cortical thickness measures were derived through an automated segmentation procedure from T1-weighted structural magnetic resonance images obtained on unsedated children. Attention was assessed using the computerized Conners’ Kiddie Continuous Performance Test Version 5 (K-CPT™ V.5). PME effects on subcortical and cortical brain volumes and cortical thickness were tested by general linear model with type III sum of squares, adjusting for PTE, prenatal marijuana exposure, age at time of scan, gender, handedness, pulse sequence and total intracranial volume (for volumetric outcomes). A similar analysis was done for PTE effects on subcortical and cortical brain volumes and thickness, adjusting for PME and the above covariates. Results Children with PME had significantly reduced caudate nucleus volumes and cortical thickness increases in perisylvian and orbital-frontal cortices. In contrast, children with PTE showed cortical thinning in perisylvian and lateral occipital cortices and volumetric increases in frontal regions and decreases in anterior cingulate. PME was positively related and caudate volume was inversely related to K-CPT reaction time by inter-stimulus interval, a measure of the ability to adjust to changing task demands, suggesting that children with PME may have subtle attentional deficits mediated by caudate volume reductions. Conclusions Our results suggest that PME and PTE may have distinct differential cortical effects on the developing central nervous system. Additionally, PME may be

  6. Effects of pharmacological agents on subcortical resistance shifts

    NASA Technical Reports Server (NTRS)

    Klivington, K. A.

    1975-01-01

    Microliter quantities of tetrodotoxin, tetraethylammonium chloride, and picrotoxin injected into the inferior colliculus and superior olive of unanesthetized cats differentially affect the amplitude and waveform of click-evoked potentials and evoked resistance shifts. Tetrodotoxin simultaneously reduces the negative phase of the evoked potential and eliminates the evoked resistance shift. Tetraethylammonium enhances the negative evoked potential component, presumably of postsynaptic origin, without significantly altering evoked resistance shift amplitude. Picrotoxin also enhances the negative evoked potential wave but increases evoked resistance shift amplitude. These findings implicate events associated with postsynaptic membrane depolarization in the production of the evoked resistance shift.

  7. Registration and machine learning-based automated segmentation of subcortical and cerebellar brain structures.

    PubMed

    Powell, Stephanie; Magnotta, Vincent A; Johnson, Hans; Jammalamadaka, Vamsi K; Pierson, Ronald; Andreasen, Nancy C

    2008-01-01

    The large amount of imaging data collected in several ongoing multi-center studies requires automated methods to delineate brain structures of interest. We have previously reported on using artificial neural networks (ANN) to define subcortical brain structures. Here we present several automated segmentation methods using multidimensional registration. A direct comparison between template, probability, artificial neural network (ANN) and support vector machine (SVM)-based automated segmentation methods is presented. Three metrics for each segmentation method are reported in the delineation of subcortical and cerebellar brain regions. Results show that the machine learning methods outperform the template and probability-based methods. Utilization of these automated segmentation methods may be as reliable as manual raters and require no rater intervention.

  8. Direct Microtubule-Binding by Myosin-10 Orients Centrosomes toward Retraction Fibers and Subcortical Actin Clouds.

    PubMed

    Kwon, Mijung; Bagonis, Maria; Danuser, Gaudenz; Pellman, David

    2015-08-10

    Positioning of centrosomes is vital for cell division and development. In metazoan cells, spindle positioning is controlled by a dynamic pool of subcortical actin that organizes in response to the position of retraction fibers. These actin "clouds" are proposed to generate pulling forces on centrosomes and mediate spindle orientation. However, the motors that pull astral microtubules toward these actin structures are not known. Here, we report that the unconventional myosin, Myo10, couples actin-dependent forces from retraction fibers and subcortical actin clouds to centrosomes. Myo10-mediated centrosome positioning requires its direct microtubule binding. Computational image analysis of large microtubule populations reveals a direct effect of Myo10 on microtubule dynamics and microtubule-cortex interactions. Myo10's role in centrosome positioning is distinct from, but overlaps with, that of dynein. Thus, Myo10 plays a key role in integrating the actin and microtubule cytoskeletons to position centrosomes and mitotic spindles.

  9. Gerstmann meets Geschwind: a crossing (or kissing) variant of a subcortical disconnection syndrome?

    PubMed

    Kleinschmidt, Andreas; Rusconi, Elena

    2011-12-01

    That disconnection causes clinical symptoms is a very influential concept in behavioral neurology. Criteria for subcortical disconnection usually are symptoms that are distinct from those following cortical lesions and damage to a single, long-range fiber tract. Yet, a recent study combining functional magnetic resonance imaging and fiber tracking concluded that a focal lesion in left parietal white matter provides the only tenable explanation for pure Gerstmann's syndrome, an enigmatic tetrad of acalculia, agraphia, finger agnosia, and left-right disorientation. Such a lesion would affect not only a single fiber tract but crossing or "kissing" of different fiber tracts and hence disconnect separate cortical networks. As fiber crossing is prominent in the cerebral white matter, the authors propose an extension to the subcortical disconnection framework that opens the door to ascribing a more diversified clinical phenomenology to white matter damage and ensuing disconnection than has been the case so far.

  10. In vivo three-photon microscopy of subcortical structures within an intact mouse brain

    NASA Astrophysics Data System (ADS)

    Horton, Nicholas G.; Wang, Ke; Kobat, Demirhan; Clark, Catharine G.; Wise, Frank W.; Schaffer, Chris B.; Xu, Chris

    2013-03-01

    Two-photon fluorescence microscopy enables scientists in various fields including neuroscience, embryology and oncology to visualize in vivo and ex vivo tissue morphology and physiology at a cellular level deep within scattering tissue. However, tissue scattering limits the maximum imaging depth of two-photon fluorescence microscopy to the cortical layer within mouse brain, and imaging subcortical structures currently requires the removal of overlying brain tissue or the insertion of optical probes. Here, we demonstrate non-invasive, high-resolution, in vivo imaging of subcortical structures within an intact mouse brain using three-photon fluorescence microscopy at a spectral excitation window of 1,700 nm. Vascular structures as well as red fluorescent protein-labelled neurons within the mouse hippocampus are imaged. The combination of the long excitation wavelength and the higher-order nonlinear excitation overcomes the limitations of two-photon fluorescence microscopy, enabling biological investigations to take place at a greater depth within tissue.

  11. Use of neuronavigation and electrophysiology in surgery of subcortically located lesions in the sensorimotor strip

    PubMed Central

    Eisner, W; Burtscher, J; Bale, R; Sweeney, R; Koppelstatter, F; Golaszewski, S; Kolbitsch, C; Twerdy, K

    2002-01-01

    Objectives: Subcortical lesions in the sensorimotor strip are often considered to be inoperable. The purpose of this study was to evaluate the usefulness of a combined approach for surgery in this region, aided by a robotic neuronavigation system under electrophysiological control. Methods: In a prospective study on 10 patients, space occupying lesions in the sensorimotor central area were removed using the Surgiscope® robotic navigation system and the Nicolet Viking IV® electrophysiological system. Results: Precise tumour localisation with the neuronavigation system and the information on the patient's cortical motor distribution obtained by bipolar cortical stimulation led to postoperative improvement in motor function in all but one patient. Seven of the patients had focal, defined pathology (four metastases; two cavernoma; one aspergilloma). Conclusion: Due to the implementation of two recent technologies, surgery of lesions in the subcortical sensorimotor region can be performed with greater confidence. PMID:11861700

  12. Genetic influences on schizophrenia and subcortical brain volumes: large-scale proof of concept.

    PubMed

    Franke, Barbara; Stein, Jason L; Ripke, Stephan; Anttila, Verneri; Hibar, Derrek P; van Hulzen, Kimm J E; Arias-Vasquez, Alejandro; Smoller, Jordan W; Nichols, Thomas E; Neale, Michael C; McIntosh, Andrew M; Lee, Phil; McMahon, Francis J; Meyer-Lindenberg, Andreas; Mattheisen, Manuel; Andreassen, Ole A; Gruber, Oliver; Sachdev, Perminder S; Roiz-Santiañez, Roberto; Saykin, Andrew J; Ehrlich, Stefan; Mather, Karen A; Turner, Jessica A; Schwarz, Emanuel; Thalamuthu, Anbupalam; Yao, Yin; Ho, Yvonne Y W; Martin, Nicholas G; Wright, Margaret J; O'Donovan, Michael C; Thompson, Paul M; Neale, Benjamin M; Medland, Sarah E; Sullivan, Patrick F

    2016-03-01

    Schizophrenia is a devastating psychiatric illness with high heritability. Brain structure and function differ, on average, between people with schizophrenia and healthy individuals. As common genetic associations are emerging for both schizophrenia and brain imaging phenotypes, we can now use genome-wide data to investigate genetic overlap. Here we integrated results from common variant studies of schizophrenia (33,636 cases, 43,008 controls) and volumes of several (mainly subcortical) brain structures (11,840 subjects). We did not find evidence of genetic overlap between schizophrenia risk and subcortical volume measures either at the level of common variant genetic architecture or for single genetic markers. These results provide a proof of concept (albeit based on a limited set of structural brain measures) and define a roadmap for future studies investigating the genetic covariance between structural or functional brain phenotypes and risk for psychiatric disorders.

  13. Early developmental gene enhancers affect subcortical volumes in the adult human brain.

    PubMed

    Becker, Martin; Guadalupe, Tulio; Franke, Barbara; Hibar, Derrek P; Renteria, Miguel E; Stein, Jason L; Thompson, Paul M; Francks, Clyde; Vernes, Sonja C; Fisher, Simon E

    2016-05-01

    Genome-wide association screens aim to identify common genetic variants contributing to the phenotypic variability of complex traits, such as human height or brain morphology. The identified genetic variants are mostly within noncoding genomic regions and the biology of the genotype-phenotype association typically remains unclear. In this article, we propose a complementary targeted strategy to reveal the genetic underpinnings of variability in subcortical brain volumes, by specifically selecting genomic loci that are experimentally validated forebrain enhancers, active in early embryonic development. We hypothesized that genetic variation within these enhancers may affect the development and ultimately the structure of subcortical brain regions in adults. We tested whether variants in forebrain enhancer regions showed an overall enrichment of association with volumetric variation in subcortical structures of >13,000 healthy adults. We observed significant enrichment of genomic loci that affect the volume of the hippocampus within forebrain enhancers (empirical P = 0.0015), a finding which robustly passed the adjusted threshold for testing of multiple brain phenotypes (cutoff of P < 0.0083 at an alpha of 0.05). In analyses of individual single nucleotide polymorphisms (SNPs), we identified an association upstream of the ID2 gene with rs7588305 and variation in hippocampal volume. This SNP-based association survived multiple-testing correction for the number of SNPs analyzed but not for the number of subcortical structures. Targeting known regulatory regions offers a way to understand the underlying biology that connects genotypes to phenotypes, particularly in the context of neuroimaging genetics. This biology-driven approach generates testable hypotheses regarding the functional biology of identified associations. Hum Brain Mapp 37:1788-1800, 2016. © 2016 Wiley Periodicals, Inc.

  14. Abnormal Subcortical Brain Morphology in Patients with Knee Osteoarthritis: A Cross-sectional Study

    PubMed Central

    Mao, Cui Ping; Bai, Zhi Lan; Zhang, Xiao Na; Zhang, Qiu Juan; Zhang, Lei

    2016-01-01

    Despite the involvement of subcortical brain structures in the pathogenesis of chronic pain and persistent pain as the defining symptom of knee osteoarthritis (KOA), little attention has been paid to the morphometric measurements of these subcortical nuclei in patients with KOA. The purpose of this study is to explore the potential morphological abnormalities of subcortical brain structures in patients with KOA as compared to the healthy control subjects by using high-resolution MRI. Structural MR data were acquired from 26 patients with KOA and 31 demographically similar healthy individuals. The MR data were analyzed by using FMRIB’s integrated registration and segmentation tool. Both volumetric analysis and surface-based shape analysis were performed to characterize the subcortical morphology. The normalized volumes of bilateral caudate nucleus were significantly smaller in the KOA group than in the control group (P = 0.004). There was also a trend toward smaller volume of the hippocampus in KOA as compared to the control group (P = 0.027). Detailed surface analyses further localized these differences with a greater involvement of the left hemisphere (P < 0.05, corrected) for the caudate nucleus. Hemispheric asymmetry (right larger than left) of the caudate nucleus was found in both KOA and control groups. Besides, no significant correlation was found between the structural data and pain intensities. Our results indicated that patients with KOA had statistically significant smaller normalized volumes of bilateral caudate nucleus and a trend toward smaller volume of the hippocampus as compared to the control subjects. Further investigations are necessary to characterize the role of caudate nucleus in the course of chronicity of pain associated with KOA. PMID:26834629

  15. Cortical and subcortical predictive dynamics and learning during perception, cognition, emotion and action

    PubMed Central

    Grossberg, Stephen

    2009-01-01

    An intimate link exists between the predictive and learning processes in the brain. Perceptual/cognitive and spatial/motor processes use complementary predictive mechanisms to learn, recognize, attend and plan about objects in the world, determine their current value, and act upon them. Recent neural models clarify these mechanisms and how they interact in cortical and subcortical brain regions. The present paper reviews and synthesizes data and models of these processes, and outlines a unified theory of predictive brain processing. PMID:19528003

  16. Measurement and genetics of human subcortical and hippocampal asymmetries in large datasets.

    PubMed

    Guadalupe, Tulio; Zwiers, Marcel P; Teumer, Alexander; Wittfeld, Katharina; Vasquez, Alejandro Arias; Hoogman, Martine; Hagoort, Peter; Fernandez, Guillen; Buitelaar, Jan; Hegenscheid, Katrin; Völzke, Henry; Franke, Barbara; Fisher, Simon E; Grabe, Hans J; Francks, Clyde

    2014-07-01

    Functional and anatomical asymmetries are prevalent features of the human brain, linked to gender, handedness, and cognition. However, little is known about the neurodevelopmental processes involved. In zebrafish, asymmetries arise in the diencephalon before extending within the central nervous system. We aimed to identify genes involved in the development of subtle, left-right volumetric asymmetries of human subcortical structures using large datasets. We first tested the feasibility of measuring left-right volume differences in such large-scale samples, as assessed by two automated methods of subcortical segmentation (FSL|FIRST and FreeSurfer), using data from 235 subjects who had undergone MRI twice. We tested the agreement between the first and second scan, and the agreement between the segmentation methods, for measures of bilateral volumes of six subcortical structures and the hippocampus, and their volumetric asymmetries. We also tested whether there were biases introduced by left-right differences in the regional atlases used by the methods, by analyzing left-right flipped images. While many bilateral volumes were measured well (scan-rescan r = 0.6-0.8), most asymmetries, with the exception of the caudate nucleus, showed lower repeatabilites. We meta-analyzed genome-wide association scan results for caudate nucleus asymmetry in a combined sample of 3,028 adult subjects but did not detect associations at genome-wide significance (P < 5 × 10(-8) ). There was no enrichment of genetic association in genes involved in left-right patterning of the viscera. Our results provide important information for researchers who are currently aiming to carry out large-scale genome-wide studies of subcortical and hippocampal volumes, and their asymmetries.

  17. [The importance of the cortex and subcortical structures of the brain in the perception of acute and chronic pain].

    PubMed

    Reschetniak, V K; Kukushkin, M L; Gurko, N S

    2014-01-01

    This review presents the current data in the literature about the importance of the cortex and subcortical structures of the brain in the perception of acute and chronic pain. Discussed the importance of various areas of the brain in perception discriminative and affective components of pain. Discusses also gender differences in pain perception depending on the functional activity of brain cortex and antinociceptive subcortical structures. Analyzed the morphological changes of cortical and subcortical structures of the brain in chronic pain syndromes. It is proved that the decrease in the volume of gray and white matter of cerebral cortex and subcortical structures is a consequence and not the cause of chronic pain syndrome. Discusses the features activate and deactivate certain areas of the cortex of the brain in acute and chronic pain. Analyzed same features the activation of several brain structures in migraine and cluster headache.

  18. Neural Correlates of Indicators of Sound Change in Cantonese: Evidence from Cortical and Subcortical Processes

    PubMed Central

    Maggu, Akshay R.; Liu, Fang; Antoniou, Mark; Wong, Patrick C. M.

    2016-01-01

    Across time, languages undergo changes in phonetic, syntactic, and semantic dimensions. Social, cognitive, and cultural factors contribute to sound change, a phenomenon in which the phonetics of a language undergo changes over time. Individuals who misperceive and produce speech in a slightly divergent manner (called innovators) contribute to variability in the society, eventually leading to sound change. However, the cause of variability in these individuals is still unknown. In this study, we examined whether such misperceptions are represented in neural processes of the auditory system. We investigated behavioral, subcortical (via FFR), and cortical (via P300) manifestations of sound change processing in Cantonese, a Chinese language in which several lexical tones are merging. Across the merging categories, we observed a similar gradation of speech perception abilities in both behavior and the brain (subcortical and cortical processes). Further, we also found that behavioral evidence of tone merging correlated with subjects' encoding at the subcortical and cortical levels. These findings indicate that tone-merger categories, that are indicators of sound change in Cantonese, are represented neurophysiologically with high fidelity. Using our results, we speculate that innovators encode speech in a slightly deviant neurophysiological manner, and thus produce speech divergently that eventually spreads across the community and contributes to sound change. PMID:28066218

  19. The dysexecutive syndrome associated with ischaemic vascular disease and related subcortical neuropathology: a Boston process approach.

    PubMed

    Lamar, Melissa; Price, Cate C; Giovannetti, Tania; Swenson, Rod; Libon, David J

    2010-01-01

    The introduction of diagnostic criteria for vascular dementia has helped to re-define the impact of various subcortical neuropathologies on aging; however, state-of-the-art neuroimaging techniques and autopsy studies suggest that not all structural brain alterations associated with vascular dementia are exclusive to this neurodegenerative process alone. Thus, a detailed analysis of the cognitive phenotype associated with ischaemic vascular disease is key to our understanding of subcortical neuropathology and its associated behaviors. Over the past twenty years, we have operationally defined this cognitive phenotype using the Boston Process Approach to neuropsychological assessment. This has led to both an empirical, as well as a theoretical understanding of three core constructs related to the dysexecutive syndrome associated with ischaemic vascular disease affecting periventricular and deep white matter as well as subcortical structures connecting these regions with the prefrontal cortex. Thus, difficulties with mental set, cognitive control and mental manipulation negatively impact executive functioning. This review will outline the subtle markers underlying this prefrontal dysfunction, i.e., the dysexecutive phenotype, associated with ischaemic vascular disease and relate it to fundamental impairments of gating subserved by basal ganglia-thalamic pathways within and across various dementia syndromes.

  20. Heritability of the shape of subcortical brain structures in the general population

    PubMed Central

    Roshchupkin, Gennady V.; Gutman, Boris A.; Vernooij, Meike W.; Jahanshad, Neda; Martin, Nicholas G.; Hofman, Albert; McMahon, Katie L.; van der Lee, Sven J.; van Duijn, Cornelia M.; de Zubicaray, Greig I.; Uitterlinden, André G.; Wright, Margaret J.; Niessen, Wiro J.; Thompson, Paul M.; Ikram, M. Arfan; Adams, Hieab H. H.

    2016-01-01

    The volumes of subcortical brain structures are highly heritable, but genetic underpinnings of their shape remain relatively obscure. Here we determine the relative contribution of genetic factors to individual variation in the shape of seven bilateral subcortical structures: the nucleus accumbens, amygdala, caudate, hippocampus, pallidum, putamen and thalamus. In 3,686 unrelated individuals aged between 45 and 98 years, brain magnetic resonance imaging and genotyping was performed. The maximal heritability of shape varies from 32.7 to 53.3% across the subcortical structures. Genetic contributions to shape extend beyond influences on intracranial volume and the gross volume of the respective structure. The regional variance in heritability was related to the reliability of the measurements, but could not be accounted for by technical factors only. These findings could be replicated in an independent sample of 1,040 twins. Differences in genetic contributions within a single region reveal the value of refined brain maps to appreciate the genetic complexity of brain structures. PMID:27976715

  1. Energy landscape analysis of the subcortical brain network unravels system properties beneath resting state dynamics.

    PubMed

    Kang, Jiyoung; Pae, Chongwon; Park, Hae-Jeong

    2017-04-01

    The configuration of the human brain system at rest, which is in a transitory phase among multistable states, remains unknown. To investigate the dynamic systems properties of the human brain at rest, we constructed an energy landscape for the state dynamics of the subcortical brain network, a critical center that modulates whole brain states, using resting state fMRI. We evaluated alterations in energy landscapes following perturbation in network parameters, which revealed characteristics of the state dynamics in the subcortical brain system, such as maximal number of attractors, unequal temporal occupations, and readiness for reconfiguration of the system. Perturbation in the network parameters, even those as small as the ones in individual nodes or edges, caused a significant shift in the energy landscape of brain systems. The effect of the perturbation on the energy landscape depended on the network properties of the perturbed nodes and edges, with greater effects on hub nodes and hubs-connecting edges in the subcortical brain system. Two simultaneously perturbed nodes produced perturbation effects showing low sensitivity in the interhemispheric homologous nodes and strong dependency on the more primary node among the two. This study demonstrated that energy landscape analysis could be an important tool to investigate alterations in brain networks that may underlie certain brain diseases, or diverse brain functions that may emerge due to the reconfiguration of the default brain network at rest.

  2. Lack of Gender Influence on Cortical and Subcortical Gray Matter Development in Childhood-Onset Schizophrenia

    PubMed Central

    Weisinger, Brian; Greenstein, Deanna; Mattai, Anand; Clasen, Liv; Lalonde, Francois; Feldman, Sara; Miller, Rachel; Tossell, Julia W.; Vyas, Nora S.; Stidd, Reva; David, Christopher; Gogtay, Nitin

    2013-01-01

    Background: Progressive cortical gray matter (GM) abnormalities are an established feature of schizophrenia and are more pronounced in rare, severe, and treatment refractory childhood-onset schizophrenia (COS) cases. The effect of sex on brain development in schizophrenia is poorly understood and studies to date have produced inconsistent results. >Methods: Using the largest to date longitudinal sample of COS cases (n = 104, scans = 249, Male/Female [M/F] = 57/47), we compared COS sex differences with sex differences in a sample of matched typically developing children (n = 104, scans = 244, M/F = 57/47), to determine whether or not sex had differential effects on cortical and subcortical brain development in COS. Results: Our results showed no significant differential sex effects in COS for either GM cortical thickness or subcortical volume development (sex × diagnosis × age interaction; false discovery rate q = 0.05). Conclusion: Sex appears to play a similar role in cortical and subcortical GM development in COS as it does in normally developing children. PMID:21613381

  3. Transulcal parafascicular minimally invasive approach to deep and subcortical cavernomas: technical note.

    PubMed

    Scranton, Robert A; Fung, Steve H; Britz, Gavin W

    2016-12-01

    Cavernomas comprise 8%-15% of intracranial vascular lesions, usually supratentorial in location and superficial. Cavernomas in the thalamus or subcortical white matter represent a unique challenge for surgeons in trying to identify and then use a safe corridor to access and resect the pathology. Previous authors have described specific open microsurgical corridors based on pathology location, often with technical difficulty and morbidity. This series presents 2 cavernomas that were resected using a minimally invasive approach that is less technically demanding and has a good safety profile. The authors report 2 cases of cavernoma: one in the thalamus and brainstem with multiple hemorrhages and the other in eloquent subcortical white matter. These lesions were resected through a transulcal parafascicular approach with a port-based minimally invasive technique. In this series there was complete resection with no neurological complications. The transulcal parafascicular minimally invasive approach relies on image interpretation and trajectory planning, intraoperative navigation, cortical cannulation and subcortical space access, high-quality optics, and resection as key elements to minimize exposure and retraction and maximize tissue preservation. The authors applied this technique to 2 patients with cavernomas in eloquent locations with excellent outcomes.

  4. Task switching in traumatic brain injury relates to cortico-subcortical integrity.

    PubMed

    Leunissen, Inge; Coxon, James P; Caeyenberghs, Karen; Michiels, Karla; Sunaert, Stefan; Swinnen, Stephan P

    2014-05-01

    Suppressing and flexibly adapting actions are a critical part of our daily behavioral repertoire. Traumatic brain injury (TBI) patients show clear impairments in this type of action control; however, the underlying mechanisms are poorly understood. Here, we tested whether white matter integrity of cortico-subcortical pathways could account for impairments in task switching, an important component of executive functioning. Twenty young adults with TBI and eighteen controls performed a switching task requiring attention to global versus local stimulus features. Diffusion weighted images were acquired and whole brain tract-based spatial statistics (TBSS) were used to explore where white matter damage was associated with switching impairment. A crossing fiber model and probabilistic tractography further identified the specific fiber populations. Relative to controls, patients with a history of TBI had a higher switch cost and were less accurate. The TBI group showed a widespread decline in fractional anisotropy (FA) throughout the TBSS skeleton. FA in the superior corona radiata showed a negative relationship with switch cost. More specifically, this involved cortico-subcortical loops with the (pre-)supplementary motor area and superior frontal gyrus. These findings provide evidence for damage to frontal-subcortical projections in TBI, which is associated with task switching impairments.

  5. Human subcortical brain asymmetries in 15,847 people worldwide reveal effects of age and sex.

    PubMed

    Guadalupe, Tulio; Mathias, Samuel R; vanErp, Theo G M; Whelan, Christopher D; Zwiers, Marcel P; Abe, Yoshinari; Abramovic, Lucija; Agartz, Ingrid; Andreassen, Ole A; Arias-Vásquez, Alejandro; Aribisala, Benjamin S; Armstrong, Nicola J; Arolt, Volker; Artiges, Eric; Ayesa-Arriola, Rosa; Baboyan, Vatche G; Banaschewski, Tobias; Barker, Gareth; Bastin, Mark E; Baune, Bernhard T; Blangero, John; Bokde, Arun L W; Boedhoe, Premika S W; Bose, Anushree; Brem, Silvia; Brodaty, Henry; Bromberg, Uli; Brooks, Samantha; Büchel, Christian; Buitelaar, Jan; Calhoun, Vince D; Cannon, Dara M; Cattrell, Anna; Cheng, Yuqi; Conrod, Patricia J; Conzelmann, Annette; Corvin, Aiden; Crespo-Facorro, Benedicto; Crivello, Fabrice; Dannlowski, Udo; de Zubicaray, Greig I; de Zwarte, Sonja M C; Deary, Ian J; Desrivières, Sylvane; Doan, Nhat Trung; Donohoe, Gary; Dørum, Erlend S; Ehrlich, Stefan; Espeseth, Thomas; Fernández, Guillén; Flor, Herta; Fouche, Jean-Paul; Frouin, Vincent; Fukunaga, Masaki; Gallinat, Jürgen; Garavan, Hugh; Gill, Michael; Suarez, Andrea Gonzalez; Gowland, Penny; Grabe, Hans J; Grotegerd, Dominik; Gruber, Oliver; Hagenaars, Saskia; Hashimoto, Ryota; Hauser, Tobias U; Heinz, Andreas; Hibar, Derrek P; Hoekstra, Pieter J; Hoogman, Martine; Howells, Fleur M; Hu, Hao; Hulshoff Pol, Hilleke E; Huyser, Chaim; Ittermann, Bernd; Jahanshad, Neda; Jönsson, Erik G; Jurk, Sarah; Kahn, Rene S; Kelly, Sinead; Kraemer, Bernd; Kugel, Harald; Kwon, Jun Soo; Lemaitre, Herve; Lesch, Klaus-Peter; Lochner, Christine; Luciano, Michelle; Marquand, Andre F; Martin, Nicholas G; Martínez-Zalacaín, Ignacio; Martinot, Jean-Luc; Mataix-Cols, David; Mather, Karen; McDonald, Colm; McMahon, Katie L; Medland, Sarah E; Menchón, José M; Morris, Derek W; Mothersill, Omar; Maniega, Susana Munoz; Mwangi, Benson; Nakamae, Takashi; Nakao, Tomohiro; Narayanaswaamy, Janardhanan C; Nees, Frauke; Nordvik, Jan E; Onnink, A Marten H; Opel, Nils; Ophoff, Roel; Paillère Martinot, Marie-Laure; Papadopoulos Orfanos, Dimitri; Pauli, Paul; Paus, Tomáš; Poustka, Luise; Reddy, Janardhan Yc; Renteria, Miguel E; Roiz-Santiáñez, Roberto; Roos, Annerine; Royle, Natalie A; Sachdev, Perminder; Sánchez-Juan, Pascual; Schmaal, Lianne; Schumann, Gunter; Shumskaya, Elena; Smolka, Michael N; Soares, Jair C; Soriano-Mas, Carles; Stein, Dan J; Strike, Lachlan T; Toro, Roberto; Turner, Jessica A; Tzourio-Mazoyer, Nathalie; Uhlmann, Anne; Hernández, Maria Valdés; van den Heuvel, Odile A; van der Meer, Dennis; van Haren, Neeltje E M; Veltman, Dick J; Venkatasubramanian, Ganesan; Vetter, Nora C; Vuletic, Daniella; Walitza, Susanne; Walter, Henrik; Walton, Esther; Wang, Zhen; Wardlaw, Joanna; Wen, Wei; Westlye, Lars T; Whelan, Robert; Wittfeld, Katharina; Wolfers, Thomas; Wright, Margaret J; Xu, Jian; Xu, Xiufeng; Yun, Je-Yeon; Zhao, JingJing; Franke, Barbara; Thompson, Paul M; Glahn, David C; Mazoyer, Bernard; Fisher, Simon E; Francks, Clyde

    2016-10-13

    The two hemispheres of the human brain differ functionally and structurally. Despite over a century of research, the extent to which brain asymmetry is influenced by sex, handedness, age, and genetic factors is still controversial. Here we present the largest ever analysis of subcortical brain asymmetries, in a harmonized multi-site study using meta-analysis methods. Volumetric asymmetry of seven subcortical structures was assessed in 15,847 MRI scans from 52 datasets worldwide. There were sex differences in the asymmetry of the globus pallidus and putamen. Heritability estimates, derived from 1170 subjects belonging to 71 extended pedigrees, revealed that additive genetic factors influenced the asymmetry of these two structures and that of the hippocampus and thalamus. Handedness had no detectable effect on subcortical asymmetries, even in this unprecedented sample size, but the asymmetry of the putamen varied with age. Genetic drivers of asymmetry in the hippocampus, thalamus and basal ganglia may affect variability in human cognition, including susceptibility to psychiatric disorders.

  6. Bilingualism at the core of the brain. Structural differences between bilinguals and monolinguals revealed by subcortical shape analysis.

    PubMed

    Burgaleta, Miguel; Sanjuán, Ana; Ventura-Campos, Noelia; Sebastian-Galles, Núria; Ávila, César

    2016-01-15

    Naturally acquiring a language shapes the human brain through a long-lasting learning and practice process. This is supported by previous studies showing that managing more than one language from early childhood has an impact on brain structure and function. However, to what extent bilingual individuals present neuroanatomical peculiarities at the subcortical level with respect to monolinguals is yet not well understood, despite the key role of subcortical gray matter for a number of language functions, including monitoring of speech production and language control - two processes especially solicited by bilinguals. Here we addressed this issue by performing a subcortical surface-based analysis in a sample of monolinguals and simultaneous bilinguals (N=88) that only differed in their language experience from birth. This analysis allowed us to study with great anatomical precision the potential differences in morphology of key subcortical structures, namely, the caudate, accumbens, putamen, globus pallidus and thalamus. Vertexwise analyses revealed significantly expanded subcortical structures for bilinguals compared to monolinguals, localized in bilateral putamen and thalamus, as well as in the left globus pallidus and right caudate nucleus. A topographical interpretation of our results suggests that a more complex phonological system in bilinguals may lead to a greater development of a subcortical brain network involved in monitoring articulatory processes.

  7. Species characterization and responses of subcortical insects to trap-logs and ethanol in a hardwood biomass plantation: Subcortical insects in hardwood plantations

    SciTech Connect

    Coyle, David R.; Brissey, Courtney L.; Gandhi, Kamal J. K.

    2015-01-02

    1. We characterized subcortical insect assemblages in economically important eastern cottonwood (Populus deltoides Bartr.), sycamore (Platanus occidentalis L.) and sweetgum (Liquidambar styraciflua L.) plantations in the southeastern U.S.A. Furthermore, we compared insect responses between freshly-cut plant material by placing traps directly over cut hardwood logs (trap-logs), traps baited with ethanol lures and unbaited (control) traps. 2. We captured a total of 15 506 insects representing 127 species in four families in 2011 and 2013. Approximately 9% and 62% of total species and individuals, respectively, and 23% and 79% of total Scolytinae species and individuals, respectively, were non-native to North America. 3. We captured more Scolytinae using cottonwood trap-logs compared with control traps in both years, although this was the case with sycamore and sweetgum only in 2013. More woodborers were captured using cottonwood and sweetgum trap-logs compared with control traps in both years, although only with sycamore in 2013. 4. Ethanol was an effective lure for capturing non-native Scolytinae; however, not all non-native species were captured using ethanol lures. Ambrosiophilus atratus (Eichhoff) and Hypothenemus crudiae (Panzer) were captured with both trap-logs and control traps, whereas Coccotrypes distinctus (Motschulsky) and Xyleborus glabratus Eichhoff were only captured on trap-logs. 5. Indicator species analysis revealed that certain scolytines [e.g. Cnestus mutilates (Blandford) and Xylosandrus crassiusculus (Motschulsky)] showed significant associations with trap-logs or ethanol baits in poplar or sweetgum trap-logs. In general, the species composition of subcortical insects, especially woodboring insects, was distinct among the three tree species and between those associated with trap-logs and control traps.

  8. Subcortical grey matter alterations in cocaine dependent individuals with substance-induced psychosis compared to non-psychotic cocaine users.

    PubMed

    Willi, Taylor S; Lang, Donna J; Honer, William G; Smith, Geoff N; Thornton, Allen E; Panenka, William J; Procyshyn, Ric M; Vila-Rodriguez, Fidel; Su, Wayne; Vertinsky, A Talia; Leonova, Olga; Rauscher, Alexander; MacEwan, G William; Barr, Alasdair M

    2016-10-01

    After prolonged psychostimulant abuse, transient psychotic symptoms referred to as "substance-induced psychosis" (SIP) can develop - closely resembling symptoms observed in schizophrenia spectrum disorders. The comparability in psychotic presentation between SIP and schizophrenias suggests that similar underlying neural deficits may contribute to the expression of psychosis across these disorders. To date, neuroanatomical characterization of grey matter structural alterations in SIP has been limited to methamphetamine associated psychosis, with no studies controlling for potential neurotoxic effects of the psychostimulant that precipitates psychosis. To investigate grey matter subcortical alterations in SIP, a voxel-based analysis of magnetic resonance images (MRI) was performed between a group of 74 cocaine dependent nonpsychotic individuals and a group of 29 individuals with cocaine-associated psychosis. The cocaine-associated psychosis group had significantly smaller volumes of the thalamus and left hippocampus, controlling for age, total brain volume, current methamphetamine dependence, and current marijuana dependence. No differences were present in bilateral caudate structures. The findings of reduced thalamic and hippocampal volumes agree with previous reports in the schizophrenia literature, suggesting alterations of these structures are not specific to schizophrenia, but may be common to multiple forms of psychosis.

  9. Glutamate Synaptic Inputs to Ventral Tegmental Area Neurons in the Rat Derive Primarily from Subcortical Sources

    PubMed Central

    Omelchenko, Natalia; Sesack, Susan R.

    2007-01-01

    Dopamine and GABA neurons in the ventral tegmental area project to the nucleus accumbens and prefrontal cortex and modulate locomotor and reward behaviors as well as cognitive and affective processes. Both midbrain cell types receive synapses from glutamate afferents that provide an essential control of behaviorally-linked activity patterns, although the sources of glutamate inputs have not yet been completely characterized. We used antibodies against the vesicular glutamate transporters VGlut1 and VGlut2 to investigate the morphology and synaptic organization of axons containing these proteins as putative markers of glutamate afferents from cortical versus subcortical sites, respectively. We also characterized the ventral tegmental area cell populations receiving VGlut1+ or VGlut2+ synapses according to their transmitter phenotype (dopamine or GABA) and major projection target (nucleus accumbens or prefrontal cortex). By light and electron microscopic examination, VGlut2+ as opposed to VGlut1+ axon terminals were more numerous, had a larger average size, synapsed more proximally, and were more likely to form convergent synapses onto the same target. Both axon types formed predominantly asymmetric synapses, although VGlut2+ terminals more often formed synapses with symmetric morphology. No absolute selectivity was observed for VGlut1+ or VGlut2+ axons to target any particular cell population. However, the synapses onto mesoaccumbens neurons more often involved VGlut2+ terminals, whereas mesoprefrontal neurons received relatively equal synaptic inputs from VGlut1+ and VGlut2+ profiles. The distinct morphological features of VGlut1 and VGlut2 positive axons suggest that glutamate inputs from presumed cortical and subcortical sources, respectively, differ in the nature and intensity of their physiological actions on midbrain neurons. More specifically, our findings imply that subcortical glutamate inputs to the ventral tegmental area expressing VGlut2 predominate over

  10. An evaluation of four automatic methods of segmenting the subcortical structures in the brain.

    PubMed

    Babalola, Kolawole Oluwole; Patenaude, Brian; Aljabar, Paul; Schnabel, Julia; Kennedy, David; Crum, William; Smith, Stephen; Cootes, Tim; Jenkinson, Mark; Rueckert, Daniel

    2009-10-01

    The automation of segmentation of subcortical structures in the brain is an active research area. We have comprehensively evaluated four novel methods of fully automated segmentation of subcortical structures using volumetric, spatial overlap and distance-based measures. Two methods are atlas-based - classifier fusion and labelling (CFL) and expectation-maximisation segmentation using a brain atlas (EMS), and two incorporate statistical models of shape and appearance - profile active appearance models (PAM) and Bayesian appearance models (BAM). Each method was applied to the segmentation of 18 subcortical structures in 270 subjects from a diverse pool varying in age, disease, sex and image acquisition parameters. Our results showed that all four methods perform on par with recently published methods. CFL performed better than the others according to all three classes of metrics. In summary over all structures, the ranking by the Dice coefficient was CFL, BAM, joint EMS and PAM. The Hausdorff distance ranked the methods as CFL, joint PAM and BAM, EMS, whilst percentage absolute volumetric difference ranked them as joint CFL and PAM, joint BAM and EMS. Furthermore, as we had four methods of performing segmentation, we investigated whether the results obtained by each method were more similar to each other than to the manual segmentations using Williams' Index. Reassuringly, the Williams' Index was close to 1 for most subjects (mean=1.02, sd=0.05), indicating better agreement of each method with the gold standard than with the other methods. However, 2% of cases (mainly amygdala and nucleus accumbens) had values outside 3 standard deviations of the mean.

  11. Adult plasticity in the subcortical auditory pathway of the maternal mouse.

    PubMed

    Miranda, Jason A; Shepard, Kathryn N; McClintock, Shannon K; Liu, Robert C

    2014-01-01

    Subcortical auditory nuclei were traditionally viewed as non-plastic in adulthood so that acoustic information could be stably conveyed to higher auditory areas. Studies in a variety of species, including humans, now suggest that prolonged acoustic training can drive long-lasting brainstem plasticity. The neurobiological mechanisms for such changes are not well understood in natural behavioral contexts due to a relative dearth of in vivo animal models in which to study this. Here, we demonstrate in a mouse model that a natural life experience with increased demands on the auditory system - motherhood - is associated with improved temporal processing in the subcortical auditory pathway. We measured the auditory brainstem response to test whether mothers and pup-naïve virgin mice differed in temporal responses to both broadband and tone stimuli, including ultrasonic frequencies found in mouse pup vocalizations. Mothers had shorter latencies for early ABR peaks, indicating plasticity in the auditory nerve and the cochlear nucleus. Shorter interpeak latency between waves IV and V also suggest plasticity in the inferior colliculus. Hormone manipulations revealed that these cannot be explained solely by estrogen levels experienced during pregnancy and parturition in mothers. In contrast, we found that pup-care experience, independent of pregnancy and parturition, contributes to shortening auditory brainstem response latencies. These results suggest that acoustic experience in the maternal context imparts plasticity on early auditory processing that lasts beyond pup weaning. In addition to establishing an animal model for exploring adult auditory brainstem plasticity in a neuroethological context, our results have broader implications for models of perceptual, behavioral and neural changes that arise during maternity, where subcortical sensorineural plasticity has not previously been considered.

  12. Central serotonin(2B) receptor blockade inhibits cocaine-induced hyperlocomotion independently of changes of subcortical dopamine outflow.

    PubMed

    Devroye, Céline; Cathala, Adeline; Di Marco, Barbara; Caraci, Filippo; Drago, Filippo; Piazza, Pier Vincenzo; Spampinato, Umberto

    2015-10-01

    The central serotonin2B receptor (5-HT2BR) is currently considered as an interesting pharmacological target for improved treatment of drug addiction. In the present study, we assessed the effect of two selective 5-HT2BR antagonists, RS 127445 and LY 266097, on cocaine-induced hyperlocomotion and dopamine (DA) outflow in the nucleus accumbens (NAc) and the dorsal striatum of freely moving rats. The peripheral administration of RS 127445 (0.16 mg/kg, i.p.) or LY 266097 (0.63 mg/kg, i.p.) significantly reduced basal DA outflow in the NAc shell, but had no effect on cocaine (10 mg/kg, i.p.)-induced DA outflow in this brain region. Also, RS 127445 failed to modify both basal and cocaine-induced DA outflow in the NAc core and the dorsal striatum. Conversely, both 5-HT2BR antagonists reduced cocaine-induced hyperlocomotion. Furthermore, RS 127445 as well as the DA-R antagonist haloperidol (0.1 mg/kg, i.p.) reduced significantly the late-onset hyperlocomotion induced by the DA-R agonist quinpirole (0.5 mg/kg, s.c.). Altogether, these results demonstrate that 5-HT2BR blockade inhibits cocaine-induced hyperlocomotion independently of changes of subcortical DA outflow. This interaction takes place downstream to DA neurons and could involve an action at the level of dorsostriatal and/or NAc DA transmission, in keeping with the importance of these brain regions in the behavioural responses of cocaine. Overall, this study affords additional knowledge into the regulatory control exerted by the 5-HT2BR on ascending DA pathways, and provides additional support to the proposed role of 5-HT2BRs as a new pharmacological target in drug addiction.

  13. Subcortical neural representation to Mandarin pitch contours in American and Chinese newborns.

    PubMed

    Jeng, Fuh-Cherng; Lin, Chia-Der; Wang, Tang-Chuan

    2016-06-01

    Voice pitch carries important information for speech understanding. This study examines the neural representation of voice pitch at the subcortical level, as reflected by the scalp-recorded frequency-following responses from ten American and ten Chinese newborns. By utilizing a set of four distinctive Mandarin pitch contours that mimic the English vowel /yi/, the results indicate that the rising and dipping pitch contours produce significantly better tracking accuracy and larger response amplitudes than the falling pitch contour. This finding suggests a hierarchy of potential stimuli when testing neonates who are born in a tonal or non-tonal linguistic environment.

  14. Complex sound stimuli representation by small neural groups in subcortical auditory structure

    NASA Astrophysics Data System (ADS)

    Lyzwa, Dominika

    The neural representation of complex natural sound stimuli in higher auditory structures is not yet well understood. Based on neurophysiological recordings from the mammalian auditory midbrain, neural responses to complex (natural and also artificial) sounds are investigated and mapped with respect to temporal and spectral neural tuning in the subcortical structure. The mapping includes spiking activity of single neurons and small neural clusters and local field potential activity. A neural model is presented which captures the mapping and also the similarity of responses across the auditory structure, and is used to predict responses to novel sound. Financial support by Bernstein Focus Neural Technology Goettingen, Grant Number #01GQ0811.

  15. More than just channeling: The role of subcortical mechanisms in executive functions - Evidence from the Stroop task.

    PubMed

    Saban, William; Gabay, Shai; Kalanthroff, Eyal

    2017-03-10

    The literature has long emphasized the role of the cerebral cortex in executive functions. Recently, however, several researchers have suggested that subcortical areas might also be involved in executive functions. The current study explored the possibility that subcortical mechanisms have a functional role in adaptive resolution of Stroop interference. We asked 20 participants to complete a cued task-switching Stroop task with variable cue-target intervals (CTI). Using a stereoscope, we manipulated which eye was shown the relevant dimension and which was shown the irrelevant dimension. This technique allowed us to examine the involvement of monocularly segregated - subcortical - regions of the visual processing stream. The interference effect was modulated by this eye-of-origin manipulation in the 0 CTI condition. This finding provides a novel indication for the notion that subcortical regions have a functional role in the resolution of Stroop interference. This indication suggests that cortical regions are not solely involved and that a dynamic interaction between cortical and subcortical regions is involved in executive functions.

  16. Reliability and statistical power analysis of cortical and subcortical FreeSurfer metrics in a large sample of healthy elderly.

    PubMed

    Liem, Franziskus; Mérillat, Susan; Bezzola, Ladina; Hirsiger, Sarah; Philipp, Michel; Madhyastha, Tara; Jäncke, Lutz

    2015-03-01

    FreeSurfer is a tool to quantify cortical and subcortical brain anatomy automatically and noninvasively. Previous studies have reported reliability and statistical power analyses in relatively small samples or only selected one aspect of brain anatomy. Here, we investigated reliability and statistical power of cortical thickness, surface area, volume, and the volume of subcortical structures in a large sample (N=189) of healthy elderly subjects (64+ years). Reliability (intraclass correlation coefficient) of cortical and subcortical parameters is generally high (cortical: ICCs>0.87, subcortical: ICCs>0.95). Surface-based smoothing increases reliability of cortical thickness maps, while it decreases reliability of cortical surface area and volume. Nevertheless, statistical power of all measures benefits from smoothing. When aiming to detect a 10% difference between groups, the number of subjects required to test effects with sufficient power over the entire cortex varies between cortical measures (cortical thickness: N=39, surface area: N=21, volume: N=81; 10mm smoothing, power=0.8, α=0.05). For subcortical regions this number is between 16 and 76 subjects, depending on the region. We also demonstrate the advantage of within-subject designs over between-subject designs. Furthermore, we publicly provide a tool that allows researchers to perform a priori power analysis and sensitivity analysis to help evaluate previously published studies and to design future studies with sufficient statistical power.

  17. Formulaic Language in Parkinson's Disease and Alzheimer's Disease: Complementary Effects of Subcortical and Cortical Dysfunction

    PubMed Central

    Van Lancker Sidtis, Diana; Choi, JiHee; Alken, Amy

    2015-01-01

    Purpose The production of formulaic expressions (conversational speech formulas, pause fillers, idioms, and other fixed expressions) is excessive in the left hemisphere and deficient in the right hemisphere and in subcortical stroke. Speakers with Alzheimer's disease (AD), having functional basal ganglia, reveal abnormally high proportions of formulaic language. Persons with Parkinson's disease (PD), having dysfunctional basal ganglia, were predicted to show impoverished formulaic expressions in contrast to speakers with AD. This study compared participants with PD, participants with AD, and healthy control (HC) participants on protocols probing production and comprehension of formulaic expressions. Method Spontaneous speech samples were recorded from 16 individuals with PD, 12 individuals with AD, and 18 HC speakers. Structured tests were then administered as probes of comprehension. Results The PD group had lower proportions of formulaic expressions compared with the AD and HC groups. Comprehension testing yielded opposite contrasts: participants with PD showed significantly higher performance compared with participants with AD and did not differ from HC participants. Conclusions The finding that PD produced lower proportions of formulaic expressions compared with AD and HC supports the view that subcortical nuclei modulate the production of formulaic expressions. Contrasting results on formal testing of comprehension, whereby participants with AD performed significantly worse than participants with PD and HC participants, indicate differential effects on procedural and declarative knowledge associated with these neurological conditions. PMID:26183940

  18. Sex Differences in Fiber Connection between the Striatum and Subcortical and Cortical Regions

    PubMed Central

    Lei, Xuemei; Han, Zhuo; Chen, Chuansheng; Bai, Lu; Xue, Gui; Dong, Qi

    2016-01-01

    The striatum is an important subcortical structure with extensive connections to other regions of the brain. These connections are believed to play important roles in behaviors such as reward-related processes and impulse control, which show significant sex differences. However, little is known about sex differences in the striatum-projected fiber connectivity. The current study examined sex differences between 50 Chinese males and 79 Chinese females in their fiber connections between the striatum and nine selected cortical and subcortical regions. Despite overall similarities, males showed stronger fiber connections between the left caudate and rostral cingulate cortex, between the right putamen and the lateral orbitofrontal cortex, between the bilateral putamen and the ventro-lateral prefrontal cortex, and between the right caudate and the ventro-lateral prefrontal cortex, whereas females showed stronger fiber connections between the right putamen and the dorsolateral prefrontal cortex, between bilateral caudate and hippocampus, and between the left putamen and hippocampus. These findings help us to understand sex differences in the striatum-projected fiber connections and their implications for sex differences in behaviors. PMID:27721750

  19. Recreational marijuana use impacts white matter integrity and subcortical (but not cortical) morphometry.

    PubMed

    Orr, Joseph M; Paschall, Courtnie J; Banich, Marie T

    2016-01-01

    A recent shift in legal and social attitudes toward marijuana use has also spawned a surge of interest in understanding the effects of marijuana use on the brain. There is considerable evidence that an adolescent onset of marijuana use negatively impacts white matter coherence. On the other hand, a recent well-controlled study demonstrated no effects of marijuana use on the morphometry of subcortical or cortical structures when users and non-users were matched for alcohol use. Regardless, most studies have involved small, carefully selected samples, so the ability to generalize to larger populations is limited. In an attempt to address this issue, we examined the effects of marijuana use on white matter integrity and cortical and subcortical morphometry using data from the Human Connectome Project (HCP) consortium. The HCP data consists of ultra-high resolution neuroimaging data from a large community sample, including 466 adults reporting recreational marijuana use. Rather than just contrasting two groups of individuals who vary significantly in marijuana usage as typifies prior studies, we leveraged the large sample size provided by the HCP data to examine parametric effects of recreational marijuana use. Our results indicate that the earlier the age of onset of marijuana use, the lower was white matter coherence. Age of onset also also affected the shape of the accumbens, while the number of lifetime uses impacted the shape of the amygdala and hippocampus. Marijuana use had no effect on cortical volumes. These findings suggest subtle but significant effects of recreational marijuana use on brain structure.

  20. Focused ultrasound neuromodulation of cortical and subcortical brain structures using 1.9 MHz

    PubMed Central

    Wang, Shutao; Chen, Hong; Wang, Qi; Aurup, Christian; Acosta, Camilo; Carneiro, Antonio A. O.; Konofagou, Elisa E.

    2016-01-01

    Purpose: Ultrasound neuromodulation is a promising noninvasive technique for controlling neural activity. Previous small animal studies suffered from low targeting specificity because of the low ultrasound frequencies (<690 kHz) used. In this study, the authors demonstrated the capability of focused ultrasound (FUS) neuromodulation in the megahertz-range to achieve superior targeting specificity in the murine brain as well as demonstrate modulation of both motor and sensory responses. Methods: FUS sonications were carried out at 1.9 MHz with 50% duty cycle, pulse repetition frequency of 1 kHz, and duration of 1 s. The robustness of the FUS neuromodulation was assessed first in sensorimotor cortex, where elicited motor activities were observed and recorded on videos and electromyography. Deeper brain regions were then targeted where pupillary dilation served as an indicative of successful modulation of subcortical brain structures. Results: Contralateral and ipsilateral movements of the hind limbs were repeatedly observed when the FUS was targeted at the sensorimotor cortex. Induced trunk and tail movements were also observed at different coordinates inside the sensorimotor cortex. At deeper targeted-structures, FUS induced eyeball movements (superior colliculus) and pupillary dilation (pretectal nucleus, locus coeruleus, and hippocampus). Histological analysis revealed no tissue damage associated with the FUS sonications. Conclusions: The motor movements and pupillary dilation observed in this study demonstrate the capability of FUS to modulate cortical and subcortical brain structures without inducing any damage. The variety of responses observed here demonstrates the capability of FUS to perform functional brain mapping. PMID:27782686

  1. Longitudinal development of cortical and subcortical gray matter from birth to 2 years.

    PubMed

    Gilmore, John H; Shi, Feng; Woolson, Sandra L; Knickmeyer, Rebecca C; Short, Sarah J; Lin, Weili; Zhu, Hongtu; Hamer, Robert M; Styner, Martin; Shen, Dinggang

    2012-11-01

    Very little is known about cortical development in the first years of life, a time of rapid cognitive development and risk for neurodevelopmental disorders. We studied regional cortical and subcortical gray matter volume growth in a group of 72 children who underwent magnetic resonance scanning after birth and at ages 1 and 2 years using a novel longitudinal registration/parcellation approach. Overall, cortical gray matter volumes increased substantially (106%) in the first year of life and less so in the second year (18%). We found marked regional differences in developmental rates, with primary motor and sensory cortices growing slower in the first year of life with association cortices growing more rapidly. In the second year of life, primary sensory regions continued to grow more slowly, while frontal and parietal regions developed relatively more quickly. The hippocampus grew less than other subcortical structures such as the amygdala and thalamus in the first year of life. It is likely that these patterns of regional gray matter growth reflect maturation and development of underlying function, as they are consistent with cognitive and functional development in the first years of life.

  2. NOTCH3 variants in patients with subcortical vascular cognitive impairment: a comparison with typical CADASIL patients.

    PubMed

    Yoon, Cindy W; Kim, Young-Eun; Seo, Sang Won; Ki, Chang-Seok; Choi, Seong Hye; Kim, Jong-Won; Na, Duk L

    2015-08-01

    Although cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is thought to be a common form of hereditary subcortical vascular cognitive impairment (SVCI), there is little data on the frequency of NOTCH3 variants in SVCI patients. We prospectively screened for NOTCH3 variants in consecutive SVCI patients who underwent brain magnetic resonance imaging and amyloid positron emission tomography as well as sequence analysis for mutational hotspots in the NOTCH3 gene. Among 117 patients with SVCI, 16 patients had either known mutations or variants of unknown significance in the NOTCH3 gene. There were no differences in clinical and neuroimaging features between SVCI patients with and without NOTCH3 variants, only except for a higher number of deep microbleeds in SVCI patients with NOTCH3 variants. Our findings suggest that there is a phenotypic entity of NOTCH3 variant that is similar to that of sporadic SVCI but not of typical CADASIL. Notably, 2 SVCI patients with NOTCH3 mutations showed significant amyloid burden, which challenges the prevailing concept that CADASIL represents the genetic model of pure small vessel disease.

  3. Sources of subcortical projections to the superior colliculus in the cat.

    PubMed

    Edwards, S B; Ginsburgh, C L; Henkel, C K; Stein, B E

    1979-03-15

    A comprehensive search for subcortical projections to the cat superior colliculus was conducted using the retrograde horseradish peroxidase (HRP) method. Over 40 different subcortical structures project to the superior colliculus. The more notable among these are grouped under the following categories. Visual structures: ventral lateral geniculate nucleus, parabigeminal nucleus, pretectal area (nucleus of the optic tract, posterior pretectal nucleus, nuclei of the posterior commissure). Auditory structures: inferior colliculus (external and pericentral nuclei), dorsomedial periolivary nucleus, nuclei of the trapezoid body, ventral nucleus of the lateral lemniscus. Somatosensory structures: sensory trigeminal complex (all divisions, but mainly the gamma division of nucleus oralis), dorsal column nuclei (mostly cuneate nucleus), and the lateral cervical nucleus. Catecholamine nuclei: locus coeruleus, raphe dorsalis, and the parabrachial nuclei. Cerebellum: medial, interposed, and lateral nuclei, and the perihypoglossal nuclei. Reticular areas: zona incerta, substantia nigra, midbrain tegmentum, nucleus paragigantocellularis lateralis, and the hypothalamus. Evidence is presented that only the parabigeminal nucleus, the nucleus of the optic tract, and the posterior pretectal nucleus project to the superficial collicular layers (striatum griseum superficiale and stratum opticum), while all other afferents terminate in the deeper layers of the colliculus. Also presented is information concerning the rostrocaudal distribution of some of these afferent connections. These findings stress the multiplicity and diversity of inputs to the deeper collicular layers, and more specifically, identify multiple sources of the physiologically well-known representations of the somatic and auditory modalities in the colliculus.

  4. Subcortical encoding of sound is enhanced in bilinguals and relates to executive function advantages

    PubMed Central

    Krizman, Jennifer; Marian, Viorica; Shook, Anthony; Skoe, Erika; Kraus, Nina

    2012-01-01

    Bilingualism profoundly affects the brain, yielding functional and structural changes in cortical regions dedicated to language processing and executive function [Crinion J, et al. (2006) Science 312:1537–1540; Kim KHS, et al. (1997) Nature 388:171–174]. Comparatively, musical training, another type of sensory enrichment, translates to expertise in cognitive processing and refined biological processing of sound in both cortical and subcortical structures. Therefore, we asked whether bilingualism can also promote experience-dependent plasticity in subcortical auditory processing. We found that adolescent bilinguals, listening to the speech syllable [da], encoded the stimulus more robustly than age-matched monolinguals. Specifically, bilinguals showed enhanced encoding of the fundamental frequency, a feature known to underlie pitch perception and grouping of auditory objects. This enhancement was associated with executive function advantages. Thus, through experience-related tuning of attention, the bilingual auditory system becomes highly efficient in automatically processing sound. This study provides biological evidence for system-wide neural plasticity in auditory experts that facilitates a tight coupling of sensory and cognitive functions. PMID:22547804

  5. White Matter Repair After Extracellular Vesicles Administration in an Experimental Animal Model of Subcortical Stroke

    PubMed Central

    Otero-Ortega, Laura; Laso-García, Fernando; Gómez-de Frutos, María del Carmen; Rodríguez-Frutos, Berta; Pascual-Guerra, Jorge; Fuentes, Blanca; Díez-Tejedor, Exuperio; Gutiérrez-Fernández, María

    2017-01-01

    Mesenchymal stem cells have previously been shown to mediate brain repair after stroke; they secrete 50–100 nm complexes called extracellular vesicles (EVs), which could be responsible for provoking neurovascular repair and functional recovery. EVs have been observed by electron microscopy and NanoSight, and they contain associated proteins such as CD81 and Alix. This purified, homogeneous population of EVs was administered intravenously after subcortical stroke in rats. To evaluate the EVs effects, we studied the biodistribution, proteomics analysis, functional evaluation, lesion size, fiber tract integrity, axonal sprouting and white matter repair markers. We found that a single administration of EVs improved functional recovery, fiber tract integrity, axonal sprouting and white matter repair markers in an experimental animal model of subcortical stroke. EVs were found in the animals’ brain and peripheral organs after euthanasia. White matter integrity was in part restored by EVs administration mediated by molecular repair factors implicated in axonal sprouting, tract connectivity, remyelination and oligodendrogenesis. These findings are associated with improved functional recovery. This novel role for EVs presents a new perspective in the development of biologics for brain repair. PMID:28300134

  6. Avoiding unseen obstacles: Subcortical vision is not sufficient to maintain normal obstacle avoidance behaviour during reaching.

    PubMed

    Ross, Alasdair I; Schenk, Thomas; Billino, Jutta; Macleod, Mary J; Hesse, Constanze

    2016-10-03

    Previous research found that a patient with cortical blindness (homonymous hemianopia) was able to successfully avoid an obstacle placed in his blind field, despite reporting no conscious awareness of it [Striemer, C. L., Chapman, C. S., & Goodale, M. A., 2009, PNAS, 106(37), 15996-16001]. This finding led to the suggestion that dorsal stream areas, that are assumed to mediate obstacle avoidance behaviour, may obtain their visual input primarily from subcortical pathways. Hence, it was suggested that normal obstacle avoidance behaviour can proceed without input from the primary visual cortex. Here we tried to replicate this finding in a group of patients (N = 6) that suffered from highly circumscribed lesions in the occipital lobe (including V1) that spared the subcortical structures that have been associated with action-blindsight. We also tested if obstacle avoidance behaviour differs depending on whether obstacles are placed only in the blind field or in both the blind and intact visual field of the patients simultaneously. As expected, all patients successfully avoided obstacles placed in their intact visual field. However, none of them showed reliable avoidance behaviour - as indicated by adjustments in the hand trajectory in response to obstacle position - for obstacles placed in their blind visual field. The effects were not dependent on whether one or two obstacles were present. These findings suggest that behaviour in complex visuomotor tasks relies on visual input from occipital areas.

  7. CADASIL Presenting as Acute Bilateral Multiple Subcortical Infarcts without a Characteristic Temporal Pole or Any External Capsule Lesions

    PubMed Central

    Ando, Takashi; Goto, Yoji; Mano, Kazuo; Ueda, Akihiko; Ando, Yukio; Mizuta, Ikuko; Mizuno, Toshiki

    2016-01-01

    A 37-year-old man was hospitalized for an evaluation of acute bilateral multiple subcortical infarcts. There were no specific signal abnormalities in the temporal pole or external capsule. An abdominal skin biopsy showed granular, electron-dense, osmiophilic material (GOM) in the smooth muscle cells on electron microscopy. A direct sequencing analysis of NOTCH3 revealed a heterozygous c.986G>A substitution in exon 6, resulting in a Cys329Tyr amino acid replacement. According to these findings, the patient was diagnosed with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencehalopathy (CADASIL). Thus, early phases of CADASIL can present as acute bilateral multiple subcortical infarcts without a characteristic temporal pole or any external capsule lesions. PMID:27725551

  8. CADASIL Presenting as Acute Bilateral Multiple Subcortical Infarcts without a Characteristic Temporal Pole or Any External Capsule Lesions.

    PubMed

    Ando, Takashi; Goto, Yoji; Mano, Kazuo; Ueda, Akihiko; Ando, Yukio; Mizuta, Ikuko; Mizuno, Toshiki

    A 37-year-old man was hospitalized for an evaluation of acute bilateral multiple subcortical infarcts. There were no specific signal abnormalities in the temporal pole or external capsule. An abdominal skin biopsy showed granular, electron-dense, osmiophilic material (GOM) in the smooth muscle cells on electron microscopy. A direct sequencing analysis of NOTCH3 revealed a heterozygous c.986G>A substitution in exon 6, resulting in a Cys329Tyr amino acid replacement. According to these findings, the patient was diagnosed with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencehalopathy (CADASIL). Thus, early phases of CADASIL can present as acute bilateral multiple subcortical infarcts without a characteristic temporal pole or any external capsule lesions.

  9. [Disorders of neurogenesis of cortical and subcortical structures in rat brain limbic system during fetal alcohol syndrome formation].

    PubMed

    Svanidze, I K; Museridze, D P; Didimova, E V; Sanikidze, T V; Gegenava, L G; Gvinadze, N N

    2012-01-01

    Disorders of neurogenesis of cortical and subcortical structures in rat brain limbic system were studied in the offspring of rats that received ethanol during pregnancy. The methods used included the staining of histological sections with cresyl violet, in vitro culture, and electron paramagnetic resonance. Prenatal alcohol intoxication was shown to induce the disturbances in proliferative activity of granular layer cells in the hippocampal dentate gyrus, neuron- and glioblast migration, enhancement of free NO and lipoperoxide production and cell death. This resulted in the changes in the number of neurons in cortical and subcortical structures of rat brain limbic system and in fetal alcohol syndrome formation.

  10. Comparison of metabolic rates, language, and memory in subcortical aphasias. [Tomographic studies using /sup 18/F-fluorodeoxyglulcose

    SciTech Connect

    Metter, E.J.; Riege, W.H.; Hanson, W.R.

    1981-01-01

    Four patients with subcortical lesions and either aphasia or amnesia were compared to four patients with cortical lesions and aphasia. Each patient had /sup 18/F-fluorodeoxyglucose positron emission computed tomography and language and memory evaluations. Metabolic depression was found in the thalamus and caudate in both groups, while only the cortical group showed cortical changes. Language changes were mild in the subcortical, while moderate to severe in the cortical group. Both groups showed severe verbal memory dysfunction. The only common abnormalities in the two groups were metabolic changes in thalamus, and severity of verbal memory dysfunction. These findings suggest a relationship between verbal memory and thalamic function.

  11. Age and Sex Related Differences in Subcortical Brain Iron Concentrations among Healthy Adults

    PubMed Central

    Persson, Ninni; Wu, Jianlin; Zhang, Qing; Liu, Ting; Shen, Jing; Bao, Ruyi; Ni, Mingfei; Liu, Tian; Wang, Yi; Spincemaille, Pascal

    2015-01-01

    Age and sex can influence brain iron levels. We studied the influence of these variables on deep gray matter magnetic susceptibilities. In 183 healthy volunteers (44.7 ± 14.2 years, range 20-69, ♀ 49%), in vivo Quantitative Susceptibility Mapping (QSM) at 1.5T was performed to estimate brain iron accumulation in the following regions of interest (ROIs): caudate nucleus (Cd), putamen (Pt), globus pallidus (Gp), thalamus (Th), pulvinar (Pul), red nucleus (Rn), substantia nigra (Sn) and the cerebellar dentate nuclei (Dn). We gauged the influence of age and sex on magnetic susceptibility by specifying a series of Structural Equation Models. The distributions of susceptibility varied in degree across the structures, conforming to histologic findings (Hallgren & Sourander, 1958), with the highest degree of susceptibility in the Gp and the lowest in the Th. Iron increase correlated across several ROIs, which may reflect an underlying age-related process. Advanced age was associated with a particularly strong linear rise of susceptibility in the striatum. Nonlinear age trends were found in the Rn, where they were the most pronounced, followed by the Pul and Sn, while minimal nonlinear trends were observed for the Pt, Th, and Dn. Moreover, sex related variations were observed, so that women showed lower levels of susceptibility in the Sn after accounting for age. Regional susceptibility of the Pul increased linearly with age in men but exhibited a nonlinear association with age in women with a leveling off starting from midlife. Women expected to be post menopause (+51 years) showed lower total magnetic susceptibility in the subcortical gray matter. The current report is consistent with previous reports of age related variations of brain iron, but also adds to the current knowledge by reporting age-related changes in less studied, smaller subcortical nuclei. This is the first in-vivo report to show lower total subcortical brain iron levels selectively in women from

  12. [Preoperative direct cortical and sub-cortical electric stimulation during cerebral surgery in functional areas].

    PubMed

    Duffau, H; Capelle, L; Sichez, J P; Bitar, A; Faillot, T; Arthuis, F; Van Effenterre, R; Fohanno, D

    1999-09-01

    Indications of surgical treatment for lesions in functional cerebral areas depend on the ratio between the definitive neurological deficit and the beneficial effect of resection. Detection of eloquent cortex is difficult because of important individual variability. Peroperative direct cortical and subcortical electrical stimulations (DCS) provide the most precise and reliable method currently available allowing identification and preservation of neurons essential for motricity, sensitivity++ and language. We report our preliminary experience with DCS in surgery of intracerebral infiltrative tumors with a consecutive series of 15 patients operated from November 96 through September 97 in our institution. Presenting symptoms in the 15 patients (8 males, 7 females, mean age 43 years) were seizures in 11 cases (73%) and neurological deficit in 4 cases (27%). Clinical examination was normal in 11 patients and revealed hemiparesia in 4. Magnetic resonance imaging (MRI) with three-dimensional reconstruction showed a precentral tumor in 10 cases, central lesion in one patient, postcentral lesion in two cases, right insular tumor (non-dominant hemisphere) in one case. All patients underwent surgical resection using DCS with detection in 13 cases of motor cortex and subcortical pathways under genera anesthesia, in one case of somatosensory area under local anesthesia, and in one case of language areas also under local anesthesia. The tumor was recurrent in two patients had been operated earlier but without DCS. Resection, verified by postoperative MRI, was total in 12 cases (80%) and estimated at 80% in 3 patients. Histological examination revealed an infiltrative glioma in 12 cases (8 low grade astrocytomas, 3 low grade oligodendrogliomas, and one anaplastic oligodendroglioma), and metastases in 3 cases. Eight patients had no postoperative deficit, while the other 7 patients were impaired, with, in all cases except one, complete recovery in 15 days to 2 months. Direct

  13. Achieved Blood Pressures in the Secondary Prevention of Small Subcortical Strokes (SPS3) Study: Challenges and Lessons Learned

    PubMed Central

    Pergola, Pablo E.; Szychowski, Jeff M.; Talbert, Robert; del Brutto, Oscar; Castellanos, Mar; Graves, John W.; Matamala, Gonzalo; Pretell, Edwin Javier; Yee, Jerry; Rebello, Rosario; Zhang, Yu; Benavente, Oscar R.

    2014-01-01

    BACKGROUND Lowering blood pressure (BP) after stroke remains a challenge, even in the context of clinical trials. The Secondary Prevention of Small Subcortical Strokes (SPS3) BP protocol, BP management during the study, and achieved BPs are described here. METHODS Patients with recent symptomatic lacunar stroke were randomized to 1 of 2 levels of systolic BP (SBP) targets: lower: <130mm Hg, or higher: 130–149mm Hg. SBP management over the course of the trial was examined by race/ethnicity and other baseline conditions. RESULTS Mean SBP decreased for both groups from baseline to the last follow-up, from 142.4 to 126.7mm Hg for the lower SBP target group and from 143.6 to 137.4mm Hg for the higher SBP target group. At baseline, participants in both groups used an average of 1.7±1.2 antihypertensive medications, which increased to a mean of 2.4±1.4 (lower group) and 1.8±1.4 (higher group) by the end-study visit. It took an average of 6 months for patients to reach their SBP target, sustained to the last follow-up. Black participants had the highest proportion of SBP ≥150mm Hg at both study entry (40%) and end-study visit (17%), as compared with whites (9%) and Hispanics (11%). CONCLUSIONS These results show that it is possible to safely lower BP even to a SBP goal <130mm Hg in a variety of patients and settings, including private and academic centers in multiple countries. This provides further support for protocol-driven care in lowering BP and consequently reducing the burden of stroke. PMID:24610884

  14. STED nanoscopy reveals the ubiquity of subcortical cytoskeleton periodicity in living neurons.

    PubMed

    D'Este, Elisa; Kamin, Dirk; Göttfert, Fabian; El-Hady, Ahmed; Hell, Stefan W

    2015-03-03

    In the axons of cultured hippocampal neurons, actin forms various structures, including bundles, patches (involved in the preservation of neuronal polarity), and a recently reported periodic ring-like structure. Nevertheless, the overlaying organization of actin in neurons and in the axon initial segment (AIS) is still unclear, due mainly to a lack of adequate imaging methods. By harnessing live-cell stimulated emission depletion (STED) nanoscopy and the fluorescent probe SiR-Actin, we show that the periodic subcortical actin structure is in fact present in both axons and dendrites. The periodic cytoskeleton organization is also found in the peripheral nervous system, specifically at the nodes of Ranvier. The actin patches in the AIS co-localize with pre-synaptic markers. Cytosolic actin organization strongly depends on the developmental stage and subcellular localization. Altogether, the results of this study reveal unique neuronal cytoskeletal features.

  15. A hypothetical mechanism for DVD: unbalanced cortical input to subcortical pathways.

    PubMed

    ten Tusscher, Marcel P M; van Rijn, Rene J

    2010-09-01

    Dissociated vertical divergence (DVD) is commonly encountered in the infantile strabismus syndrome. The movement is said to be dissociated since alignment differs between right and left eye fixation. It has been hypothesized that DVD is caused by a primitive reflex present in fish. Visual pathways in the fish brain indeed are dissociated with complete crossing at the optic chiasm and projection to the superior colliculus instead of a visual cortex. Neuroanatomical data and clinical characteristics of DVD, however, contradict this hypothesis. From these data a new hypothesis arises: corticotectal lateralization. The absence of binocular development in the cerebral cortex in infantile strabismus gives rise to dissociated activation of subcortical pathways through individual less tightly linked colliculi.

  16. Atlas image labeling of subcortical structures and vascular territories in brain CT images.

    PubMed

    Du, Kaifang; Zhang, Li; Nguyen, Tony; Ordy, Vincent; Fichte, Heinz; Ditt, Hendrik; Chefd'hotel, Christophe

    2013-01-01

    We propose a multi-atlas labeling method for subcortical structures and cerebral vascular territories in brain CT images. Each atlas image is registered to the query image by a non-rigid registration and the deformation is then applied to the labeling of the atlas image to obtain the labeling of the query image. Four label fusion strategies (single atlas, most similar atlas, major voting, and STAPLE) were compared. Image similarity values in non-rigid registration were calculated and used to select and rank atlases. Major voting fusion strategy gave the best accuracy, with DSC (Dice similarity coefficient) around 0.85 ± 0.03 for caudate, putamen, and thalamus. The experimental results also show that fusing more atlases does not necessarily yield higher accuracy and we should be able to improve accuracy and decrease computation cost at the same time by selecting a preferred set with the minimum number of atlases.

  17. Cognitive changes after stem cell transplantation in a patient with subcortical stroke.

    PubMed

    Bringas, Maria L; Suarez, Carlos; Sanchez, Carlos; Alvarez, Lazaro M; Valdes, Pedro; Salazar, Sonia; Chongo, Dora; Jahanshahi, Marjan

    2011-07-28

    The authors report a case of a 55-year-old Caucasian woman who received autologous bone marrow stem cell transplantation 3 years after a subcortical stroke. She exhibited positive cognitive changes 6 months and 1 year after the surgery without rehabilitation. The blood flow changes, measured with SPECT, were statistical significant in prefrontal areas. During the presurgical neuropsychological assessment, the patient presented a critical speech reduction, reflected in impaired performance in verbal fluency, vocabulary and in each task which required overt verbal response. One year later, she showed improvement in mental flexibility, receptive language, phonological fluency, verbal memory and auditory verbal memory. Positive cognitive changes in verbal and executive functions seem to be contingent on increased blood flow in prefrontal areas. Posterior neuropsychological evaluation 3 and 5 years after transplantation did not show deterioration of the cognitive improvement.

  18. Regionally selective atrophy of subcortical structures in prodromal HD as revealed by statistical shape analysis

    PubMed Central

    Younes, Laurent; Ratnanather, J. Tilak; Brown, Timothy; Aylward, Elizabeth; Nopoulos, Peg; Johnson, Hans; Magnotta, Vincent A.; Paulsen, Jane S.; Margolis, Russell L.; Albin, Roger L.; Miller, Michael I.; Ross, Christopher A.; Investigators, PREDICT-HD

    2013-01-01

    Huntington disease is a neurodegenerative disorder that involves preferential atrophy in the striatal complex and related subcortical nuclei. In this paper, which is based on a dataset extracted from the PREDICT-HD study, we use statistical shape analysis with deformation markers obtained through Large Deformation Diffeomorphic Metric Mapping of cortical surfaces to highlight specific atrophy patterns in the caudate, putamen, and globus pallidus, at different prodromal stages of the disease. Based on the relation to cortico-basal-ganglia circuitry, we propose that statistical shape analysis, along with other structural and functional imaging studies, may help expand our understanding of the brain circuitry affected and other aspects of the neurobiology of HD, and also guide the most effective strategies for intervention. PMID:23281100

  19. Imaging characteristics of cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL)

    PubMed Central

    Stojanov, Dragan; Aracki-Trenkic, Aleksandra; Vojinovic, Slobodan; Ljubisavljevic, Srdjan; Benedeto-Stojanov, Daniela; Tasic, Aleksandar; Vujnovic, Sasa

    2015-01-01

    Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) is an autosomal dominant vascular disorder. Diagnosis and follow-up in patients with CADASIL are based mainly on magnetic resonance imaging (MRI). MRI shows white matter hyperintensities (WMHs), lacunar infarcts and cerebral microbleeds (CMBs). WMHs lesions tend to be symmetrical and bilateral, distributed in the periventricular and deep white matter. The anterior temporal lobe and external capsules are predilection sites for WMHs, with higher specificity and sensitivity of anterior temporal lobe involvement compared to an external capsule involvement. Lacunar infarcts are presented by an imaging signal that has intensity of cerebrospinal fluid in all MRI sequences. They are localized within the semioval center, thalamus, basal ganglia and pons. CMBs are depicted as focal areas of signal loss on T2 images which increases in size on the T2*-weighted gradient echo planar images (“blooming effect”). PMID:25725137

  20. Maternally expressed NLRP2 links the subcortical maternal complex (SCMC) to fertility, embryogenesis and epigenetic reprogramming

    PubMed Central

    Mahadevan, Sangeetha; Sathappan, Varsha; Utama, Budi; Lorenzo, Isabel; Kaskar, Khalied; Van den Veyver, Ignatia B.

    2017-01-01

    Mammalian parental genomes contribute differently to early embryonic development. Before activation of the zygotic genome, the maternal genome provides all transcripts and proteins required for the transition from a highly specialized oocyte to a pluripotent embryo. Depletion of these maternally-encoded transcripts frequently results in failure of preimplantation embryonic development, but their functions in this process are incompletely understood. We found that female mice lacking NLRP2 are subfertile because of early embryonic loss and the production of fewer offspring that have a wide array of developmental phenotypes and abnormal DNA methylation at imprinted loci. By demonstrating that NLRP2 is a member of the subcortical maternal complex (SCMC), an essential cytoplasmic complex in oocytes and preimplantation embryos with poorly understood function, we identified imprinted postzygotic DNA methylation maintenance, likely by directing subcellular localization of proteins involved in this process, such as DNMT1, as a new crucial role of the SCMC for mammalian reproduction. PMID:28317850

  1. Recovery from aphasia and neglect after subcortical stroke: neuropsychological and cerebral perfusion study.

    PubMed Central

    Vallar, G; Perani, D; Cappa, S F; Messa, C; Lenzi, G L; Fazio, F

    1988-01-01

    Cortical regional cerebral perfusion was assessed by N, N, N1-trimethyl-N1-(2)-hydroxy-3-methyl-5-(I-123) iodobenzyl-1, 3-propanediamine 2 HCl I-123 (HIPDM) and single photon emission computerised tomography (SPECT) in six aphasic and two neglect patients with unilateral subcortical vascular lesions. Assessments were carried out both in the acute phase and after a period ranging from 1 to 6 months after stroke onset. In all patients an almost complete spontaneous recovery occurred and was associated with a significant improvement of cortical perfusion. A relationship between severity of aphasia and degree of cortical hypoperfusion was found, in both the acute and the follow up assessments, in the aphasic subgroup. Images PMID:2465386

  2. Language experience differentiates prefrontal and subcortical activation of the cognitive control network in novel word learning

    PubMed Central

    King, Kelly E.; Hernandez, Arturo E.

    2012-01-01

    The purpose of this study was to examine the cognitive control mechanisms in adult English speaking monolinguals compared to early sequential Spanish-English bilinguals during the initial stages of novel word learning. Functional magnetic resonance imaging during a lexico-semantic task after only two hours of exposure to novel German vocabulary flashcards showed that monolinguals activated a broader set of cortical control regions associated with higher-level cognitive processes, including the supplementary motor area (SMA), anterior cingulate (ACC), and dorsolateral prefrontal cortex (DLPFC), as well as the caudate, implicated in cognitive control of language. However, bilinguals recruited a more localized subcortical network that included the putamen, associated more with motor control of language. These results suggest that experience managing multiple languages may differentiate the learning strategy and subsequent neural mechanisms of cognitive control used by bilinguals compared to monolinguals in the early stages of novel word learning. PMID:23194816

  3. A cortico-subcortical model for generation of spatially accurate sequential saccades.

    PubMed

    Dominey, P F; Arbib, M A

    1992-01-01

    This article provides a systems framework for the analysis of cortical and subcortical interactions in the control of saccadic eye movements, A major thesis of this model is that a topography of saccade direction and amplitude is preserved through multiple projections between brain regions until they are finally transformed into a temporal pattern of activity that drives the eyes to the target. The control of voluntary saccades to visual and remembered targets is modeled in terms of interactions between posterior parietal cortex, frontal eye fields, the basal ganglia (caudate and substantia nigra), superior colliculus, mediodorsal thalamus, and the saccade generator of the brainstem. Interactions include the modulation of eye movement motor error maps by topographic inhibitory projections, dynamic remapping of spatial target representations in saccade motor error maps, and sustained neural activity that embodies spatial memory. Models of these mechanisms implemented in our Neural Simulation Language simulate behavior and neural activity described in the literature, and suggest new experiments.

  4. Derivation of a Novel Efficient Supervised Learning Algorithm from Cortical-Subcortical Loops

    PubMed Central

    Chandrashekar, Ashok; Granger, Richard

    2012-01-01

    Although brain circuits presumably carry out powerful perceptual algorithms, few instances of derived biological methods have been found to compete favorably against algorithms that have been engineered for specific applications. We forward a novel analysis of a subset of functions of cortical–subcortical loops, which constitute more than 80% of the human brain, thus likely underlying a broad range of cognitive functions. We describe a family of operations performed by the derived method, including a non-standard method for supervised classification, which may underlie some forms of cortically dependent associative learning. The novel supervised classifier is compared against widely used algorithms for classification, including support vector machines (SVM) and k-nearest neighbor methods, achieving corresponding classification rates – at a fraction of the time and space costs. This represents an instance of a biologically derived algorithm comparing favorably against widely used machine learning methods on well-studied tasks. PMID:22291632

  5. Subcortical laminar heterotopia in two sisters and their mother: MRI, clinical findings and pathogenesis.

    PubMed

    van der Valk, P H; Snoeck, I; Meiners, L C; des Portes, V; Chelly, J; Pinard, J M; Ippel, P F; van Nieuwenhuizen, O; Peters, A C

    1999-06-01

    MR imaging, clinical data and underlying pathogenesis of subcortical laminar heterotopia (SCLH), also known as band heterotopia, in two sisters and their mother are presented. On MR imaging a different degree of SCLH was found in all three affected family-members. The inversion recovery sequence was considered most useful in the demonstration of the heterotopic band of gray matter and the assessment of cortical thickness. The younger sister presented with epileptic seizures at the age of five months and a delayed achievement of developmental milestones. The older sister of seven years had epileptic seizures since the age of one year, and developmental delay. Their mother has only had one seizure-like episode at the age of 39. Her psychomotor development had been normal. Investigation of DNA samples of the three female family-members revealed a mutation in the X-linked doublecortin gene. Within families with band heterotopia, this gene has also been related to male family members with lissencephaly.

  6. An unusual case of cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy with occipital lobe involvement

    PubMed Central

    Trikamji, Bhavesh; Thomas, Mariam; Hathout, Gasser; Mishra, Shrikant

    2016-01-01

    Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an autosomal dominant angiopathy caused by a mutation in the notch 3 gene on chromosome 19. Clinically, patients may be asymptomatic or can present with recurrent ischemic episodes and strokes leading to dementia, depression, pseudobulbar palsy, and hemi- or quadraplegia. Additional manifestations that have been described include migraine (mostly with aura), psychiatric disturbances, and epileptic seizures. Neuroimaging is essential to the diagnosis of CADASIL. On imaging CADASIL is characterized by symmetric involvement by confluent lesions located subcortically in the frontal and temporal lobes as well as in the insula, periventricularly, in the centrum semiovale, in the internal and external capsule, basal ganglia, and brain stem; with relative sparing of the fronto-orbital and the occipital subcortical regions. We describe a 49 year old male with CADASIL with absence of temporal lobe findings on MRI but predominant lesions within the periventricular white matter, occipital lobes with extension into the subcortical frontal lobes, corpus callosum and cerebellar white matter. Although CADASIL characteristically presents with anterior temporal lobe involvement, these findings may be absent and our case addresses the atypical imaging findings in CADASIL. PMID:27293347

  7. Association of polygenic risk for major psychiatric illness with subcortical volumes and white matter integrity in UK Biobank

    PubMed Central

    Reus, L. M.; Shen, X.; Gibson, J.; Wigmore, E.; Ligthart, L.; Adams, M. J.; Davies, G.; Cox, S. R.; Hagenaars, S. P.; Bastin, M. E.; Deary, I. J.; Whalley, H. C.; McIntosh, A. M.

    2017-01-01

    Major depressive disorder (MDD), schizophrenia (SCZ) and bipolar disorder (BP) are common, disabling and heritable psychiatric diseases with a complex overlapping polygenic architecture. Individuals with these disorders, as well as their unaffected relatives, show widespread structural differences in corticostriatal and limbic networks. Structural variation in many of these brain regions is also heritable and polygenic but whether their genetic architecture overlaps with that of major psychiatric disorders is unknown. We sought to address this issue by examining the impact of polygenic risk of MDD, SCZ, and BP on subcortical brain volumes and white matter (WM) microstructure in a large single sample of neuroimaging data; the UK Biobank Imaging study. The first release of UK Biobank imaging data comprised participants with overlapping genetic data and subcortical volumes (N = 978) and WM measures (N = 816). The calculation of polygenic risk scores was based on genome-wide association study results generated by the Psychiatric Genomics Consortium. Our findings indicated no statistically significant associations between either subcortical volumes or WM microstructure, and polygenic risk for MDD, SCZ or BP. These findings suggest that subcortical brain volumes and WM microstructure may not be closely linked to the genetic mechanisms of major psychiatric disorders. PMID:28186152

  8. Multi-atlas segmentation of subcortical brain structures via the AutoSeg software pipeline.

    PubMed

    Wang, Jiahui; Vachet, Clement; Rumple, Ashley; Gouttard, Sylvain; Ouziel, Clémentine; Perrot, Emilie; Du, Guangwei; Huang, Xuemei; Gerig, Guido; Styner, Martin

    2014-01-01

    Automated segmenting and labeling of individual brain anatomical regions, in MRI are challenging, due to the issue of individual structural variability. Although atlas-based segmentation has shown its potential for both tissue and structure segmentation, due to the inherent natural variability as well as disease-related changes in MR appearance, a single atlas image is often inappropriate to represent the full population of datasets processed in a given neuroimaging study. As an alternative for the case of single atlas segmentation, the use of multiple atlases alongside label fusion techniques has been introduced using a set of individual "atlases" that encompasses the expected variability in the studied population. In our study, we proposed a multi-atlas segmentation scheme with a novel graph-based atlas selection technique. We first paired and co-registered all atlases and the subject MR scans. A directed graph with edge weights based on intensity and shape similarity between all MR scans is then computed. The set of neighboring templates is selected via clustering of the graph. Finally, weighted majority voting is employed to create the final segmentation over the selected atlases. This multi-atlas segmentation scheme is used to extend a single-atlas-based segmentation toolkit entitled AutoSeg, which is an open-source, extensible C++ based software pipeline employing BatchMake for its pipeline scripting, developed at the Neuro Image Research and Analysis Laboratories of the University of North Carolina at Chapel Hill. AutoSeg performs N4 intensity inhomogeneity correction, rigid registration to a common template space, automated brain tissue classification based skull-stripping, and the multi-atlas segmentation. The multi-atlas-based AutoSeg has been evaluated on subcortical structure segmentation with a testing dataset of 20 adult brain MRI scans and 15 atlas MRI scans. The AutoSeg achieved mean Dice coefficients of 81.73% for the subcortical structures.

  9. Cortical and subcortical processing of short duration speech stimuli in trained rock musicians: a pilot study.

    PubMed

    Kumar, Prawin; Anil, Sam Publius; Grover, Vibhu; Sanju, Himanshu Kumar; Sinha, Sachchidanand

    2017-02-01

    Most trained musicians are actively involved in rigorous practice from several years to achieve a high level of proficiency. Therefore, musicians are best group to research changes or modification in brain structures and functions across several information processing systems. This study aimed to investigate cortical and subcortical processing of short duration speech stimuli in trained rock musicians and non-musicians. Two groups of participant (experimental and control groups) in the age range of 18-25 years were selected for the study. Experimental group includes 15 rock musicians who had minimum professional training of 5 years of rock music, and each member had to be a regular performer of rock music for at least 15 h a week. Further age-matched 15 participants who were not having any formal training of any music served as non-musicians, in the control group. The speech-evoked ABR (S-ABR) and speech-evoked ALLR (S-LLR) with short duration speech 'synthetic /da/' was elicited in both groups. Different measures were analyzed for S-ABR and S-LLR. For S-ABR, MANOVA revealed significant main effect of groups on latencies of wave V, wave A, and amplitude of wave V/A slope. Similarly, Kruskal-Wallis test showed significantly higher F 0 amplitude in rock musicians compared with non-musicians. For S-LLR, MANOVA showed statistically significant differences observed for latencies of wave P2 and N2 and amplitude measures of P2-N2 amplitude. This study indicated better neural processing of short duration speech stimuli at subcortical as well as cortical level among rock musicians when compared with non-musicians.

  10. Monocytes and macrophages as biomarkers for the diagnosis of megalencephalic leukoencephalopathy with subcortical cysts.

    PubMed

    Petrini, Stefania; Minnone, Gaetana; Coccetti, Marianna; Frank, Claudio; Aiello, Chiara; Cutarelli, Alessandro; Ambrosini, Elena; Lanciotti, Angela; Brignone, Maria Stefania; D'Oria, Valentina; Strippoli, Raffaele; De Benedetti, Fabrizio; Bertini, Enrico; Bracci-Laudiero, Luisa

    2013-09-01

    Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare congenital leukodystrophy characterized by macrocephaly, subcortical cysts and demyelination. The majority of patients harbor mutations in the MLC1 gene encoding for a membrane protein with largely unknown function. Mutations in MLC1 hamper its normal trafficking and distribution in cell membranes, leading to enhanced degradation. MLC1 protein is highly expressed in brain astrocytes and in circulating blood cells, particularly monocytes. We used these easily available cells and monocyte-derived macrophages from healthy donors and MLC1-mutated patients to study MLC1 expression and localization, and to investigate how defective MLC1 mutations may affect macrophage functions. RT-PCR, western blot and immunofluorescence analyses show that MLC1 is expressed in both monocytes and macrophages, and its biosynthesis follows protein trafficking between endoplasmic reticulum and trans-Golgi network and the secretory pathway to the cell surface. MLC1 is transported along the endosomal recycling pathway passing through Rab5+ and Rab11A+vesicles before lysosomal degradation. Alterations in MLC1 trafficking and distribution were observed in macrophages from MLC1-mutated patients, which also showed changes in the expression and localization of several proteins involved in plasma membrane permeability, ion and water homeostasis and ion-regulated exocytosis. As a consequence of these alterations, patient-derived macrophages show abnormal cell morphology and intracellular calcium influx and altered response to hypo-osmotic stress. Our results suggest that blood-derived macrophages may give relevant information on MLC1 function and may be considered as valid biomarkers for MLC diagnosis and for investigating therapeutic strategies aimed to restore MLC1 trafficking in patient cells.

  11. Cognitively Engaging Activity Is Associated with Greater Cortical and Subcortical Volumes

    PubMed Central

    Seider, Talia R.; Fieo, Robert A.; O’Shea, Andrew; Porges, Eric C.; Woods, Adam J.; Cohen, Ronald A.

    2016-01-01

    As the population ages and dementia becomes a growing healthcare concern, it is increasingly important to identify targets for intervention to delay or attenuate cognitive decline. Research has shown that the most successful interventions aim at altering lifestyle factors. Thus, this study examined how involvement in physical, cognitive, and social activity is related to brain structure in older adults. Sixty-five adults (mean age = 71.4 years, standard deviation = 8.9) received the Community Healthy Activities Model Program for Seniors (CHAMPS), a questionnaire that polls everyday activities in which older adults may be involved, and also underwent structural magnetic resonance imaging. Stepwise regression with backward selection was used to predict weekly time spent in either social, cognitive, light physical, or heavy physical activity from the volume of one of the cortical or subcortical regions of interest (corrected by intracranial volume) as well as age, education, and gender as control variables. Regressions revealed that more time spent in cognitive activity was associated with greater volumes of all brain regions studied: total cortex (β = 0.289, p = 0.014), frontal (β = 0.276, p = 0.019), parietal (β = 0.305, p = 0.009), temporal (β = 0.275, p = 0.020), and occipital (β = 0.256, p = 0.030) lobes, and thalamus (β = 0.310, p = 0.010), caudate (β = 0.233, p = 0.049), hippocampus (β = 0.286, p = 0.017), and amygdala (β = 0.336, p = 0.004). These effects remained even after accounting for the positive association between cognitive activity and education. No other activity variable was associated with brain volumes. Results indicate that time spent in cognitively engaging activity is associated with greater cortical and subcortical brain volume. Findings suggest that interventions aimed at increasing levels of cognitive activity may delay cognitive consequences of aging and decrease the risk of developing dementia. PMID:27199740

  12. Sustained Cortical and Subcortical Measures of Auditory and Visual Plasticity following Short-Term Perceptual Learning

    PubMed Central

    Katyal, Sucharit; Engel, Stephen A.; Oxenham, Andrew J.

    2017-01-01

    Short-term training can lead to improvements in behavioral discrimination of auditory and visual stimuli, as well as enhanced EEG responses to those stimuli. In the auditory domain, fluency with tonal languages and musical training has been associated with long-term cortical and subcortical plasticity, but less is known about the effects of shorter-term training. This study combined electroencephalography (EEG) and behavioral measures to investigate short-term learning and neural plasticity in both auditory and visual domains. Forty adult participants were divided into four groups. Three groups trained on one of three tasks, involving discrimination of auditory fundamental frequency (F0), auditory amplitude modulation rate (AM), or visual orientation (VIS). The fourth (control) group received no training. Pre- and post-training tests, as well as retention tests 30 days after training, involved behavioral discrimination thresholds, steady-state visually evoked potentials (SSVEP) to the flicker frequencies of visual stimuli, and auditory envelope-following responses simultaneously evoked and measured in response to rapid stimulus F0 (EFR), thought to reflect subcortical generators, and slow amplitude modulation (ASSR), thought to reflect cortical generators. Enhancement of the ASSR was observed in both auditory-trained groups, not specific to the AM-trained group, whereas enhancement of the SSVEP was found only in the visually-trained group. No evidence was found for changes in the EFR. The results suggest that some aspects of neural plasticity can develop rapidly and may generalize across tasks but not across modalities. Behaviorally, the pattern of learning was complex, with significant cross-task and cross-modal learning effects. PMID:28107359

  13. Subcortical brain alterations in major depressive disorder: findings from the ENIGMA Major Depressive Disorder working group

    PubMed Central

    Schmaal, L; Veltman, D J; van Erp, T G M; Sämann, P G; Frodl, T; Jahanshad, N; Loehrer, E; Tiemeier, H; Hofman, A; Niessen, W J; Vernooij, M W; Ikram, M A; Wittfeld, K; Grabe, H J; Block, A; Hegenscheid, K; Völzke, H; Hoehn, D; Czisch, M; Lagopoulos, J; Hatton, S N; Hickie, I B; Goya-Maldonado, R; Krämer, B; Gruber, O; Couvy-Duchesne, B; Rentería, M E; Strike, L T; Mills, N T; de Zubicaray, G I; McMahon, K L; Medland, S E; Martin, N G; Gillespie, N A; Wright, M J; Hall, G B; MacQueen, G M; Frey, E M; Carballedo, A; van Velzen, L S; van Tol, M J; van der Wee, N J; Veer, I M; Walter, H; Schnell, K; Schramm, E; Normann, C; Schoepf, D; Konrad, C; Zurowski, B; Nickson, T; McIntosh, A M; Papmeyer, M; Whalley, H C; Sussmann, J E; Godlewska, B R; Cowen, P J; Fischer, F H; Rose, M; Penninx, B W J H; Thompson, P M; Hibar, D P

    2016-01-01

    The pattern of structural brain alterations associated with major depressive disorder (MDD) remains unresolved. This is in part due to small sample sizes of neuroimaging studies resulting in limited statistical power, disease heterogeneity and the complex interactions between clinical characteristics and brain morphology. To address this, we meta-analyzed three-dimensional brain magnetic resonance imaging data from 1728 MDD patients and 7199 controls from 15 research samples worldwide, to identify subcortical brain volumes that robustly discriminate MDD patients from healthy controls. Relative to controls, patients had significantly lower hippocampal volumes (Cohen's d=−0.14, % difference=−1.24). This effect was driven by patients with recurrent MDD (Cohen's d=−0.17, % difference=−1.44), and we detected no differences between first episode patients and controls. Age of onset ⩽21 was associated with a smaller hippocampus (Cohen's d=−0.20, % difference=−1.85) and a trend toward smaller amygdala (Cohen's d=−0.11, % difference=−1.23) and larger lateral ventricles (Cohen's d=0.12, % difference=5.11). Symptom severity at study inclusion was not associated with any regional brain volumes. Sample characteristics such as mean age, proportion of antidepressant users and proportion of remitted patients, and methodological characteristics did not significantly moderate alterations in brain volumes in MDD. Samples with a higher proportion of antipsychotic medication users showed larger caudate volumes in MDD patients compared with controls. This currently largest worldwide effort to identify subcortical brain alterations showed robust smaller hippocampal volumes in MDD patients, moderated by age of onset and first episode versus recurrent episode status. PMID:26122586

  14. Subcortical brain alterations in major depressive disorder: findings from the ENIGMA Major Depressive Disorder working group.

    PubMed

    Schmaal, L; Veltman, D J; van Erp, T G M; Sämann, P G; Frodl, T; Jahanshad, N; Loehrer, E; Tiemeier, H; Hofman, A; Niessen, W J; Vernooij, M W; Ikram, M A; Wittfeld, K; Grabe, H J; Block, A; Hegenscheid, K; Völzke, H; Hoehn, D; Czisch, M; Lagopoulos, J; Hatton, S N; Hickie, I B; Goya-Maldonado, R; Krämer, B; Gruber, O; Couvy-Duchesne, B; Rentería, M E; Strike, L T; Mills, N T; de Zubicaray, G I; McMahon, K L; Medland, S E; Martin, N G; Gillespie, N A; Wright, M J; Hall, G B; MacQueen, G M; Frey, E M; Carballedo, A; van Velzen, L S; van Tol, M J; van der Wee, N J; Veer, I M; Walter, H; Schnell, K; Schramm, E; Normann, C; Schoepf, D; Konrad, C; Zurowski, B; Nickson, T; McIntosh, A M; Papmeyer, M; Whalley, H C; Sussmann, J E; Godlewska, B R; Cowen, P J; Fischer, F H; Rose, M; Penninx, B W J H; Thompson, P M; Hibar, D P

    2016-06-01

    The pattern of structural brain alterations associated with major depressive disorder (MDD) remains unresolved. This is in part due to small sample sizes of neuroimaging studies resulting in limited statistical power, disease heterogeneity and the complex interactions between clinical characteristics and brain morphology. To address this, we meta-analyzed three-dimensional brain magnetic resonance imaging data from 1728 MDD patients and 7199 controls from 15 research samples worldwide, to identify subcortical brain volumes that robustly discriminate MDD patients from healthy controls. Relative to controls, patients had significantly lower hippocampal volumes (Cohen's d=-0.14, % difference=-1.24). This effect was driven by patients with recurrent MDD (Cohen's d=-0.17, % difference=-1.44), and we detected no differences between first episode patients and controls. Age of onset ⩽21 was associated with a smaller hippocampus (Cohen's d=-0.20, % difference=-1.85) and a trend toward smaller amygdala (Cohen's d=-0.11, % difference=-1.23) and larger lateral ventricles (Cohen's d=0.12, % difference=5.11). Symptom severity at study inclusion was not associated with any regional brain volumes. Sample characteristics such as mean age, proportion of antidepressant users and proportion of remitted patients, and methodological characteristics did not significantly moderate alterations in brain volumes in MDD. Samples with a higher proportion of antipsychotic medication users showed larger caudate volumes in MDD patients compared with controls. This currently largest worldwide effort to identify subcortical brain alterations showed robust smaller hippocampal volumes in MDD patients, moderated by age of onset and first episode versus recurrent episode status.

  15. Subcortical neuronal ensembles: an analysis of motor task association, tremor, oscillations, and synchrony in human patients.

    PubMed

    Hanson, Timothy L; Fuller, Andrew M; Lebedev, Mikhail A; Turner, Dennis A; Nicolelis, Miguel A L

    2012-06-20

    Deep brain stimulation (DBS) has expanded as an effective treatment for motor disorders, providing a valuable opportunity for intraoperative recording of the spiking activity of subcortical neurons. The properties of these neurons and their potential utility in neuroprosthetic applications are not completely understood. During DBS surgeries in 25 human patients with either essential tremor or Parkinson's disease, we acutely recorded the single-unit activity of 274 ventral intermediate/ventral oralis posterior motor thalamus (Vim/Vop) neurons and 123 subthalamic nucleus (STN) neurons. These subcortical neuronal ensembles (up to 23 neurons sampled simultaneously) were recorded while the patients performed a target-tracking motor task using a cursor controlled by a haptic glove. We observed that modulations in firing rate of a substantial number of neurons in both Vim/Vop and STN represented target onset, movement onset/direction, and hand tremor. Neurons in both areas exhibited rhythmic oscillations and pairwise synchrony. Notably, all tremor-associated neurons exhibited synchrony within the ensemble. The data further indicate that oscillatory (likely pathological) neurons and behaviorally tuned neurons are not distinct but rather form overlapping sets. Whereas previous studies have reported a linear relationship between power spectra of neuronal oscillations and hand tremor, we report a nonlinear relationship suggestive of complex encoding schemes. Even in the presence of this pathological activity, linear models were able to extract motor parameters from ensemble discharges. Based on these findings, we propose that chronic multielectrode recordings from Vim/Vop and STN could prove useful for further studying, monitoring, and even treating motor disorders.

  16. Gender-Specific Degeneration of Dementia-Related Subcortical Structures Throughout the Lifespan.

    PubMed

    Nemeth, Viola Luca; Must, Anita; Horvath, Szatmar; Király, Andras; Kincses, Zsigmond Tamas; Vécsei, László

    2017-01-01

    Age-related changes in brain structure are a question of interest to a broad field of research. Structural decline has been consistently, but not unambiguously, linked to functional consequences, including cognitive impairment and dementia. One of the areas considered of crucial importance throughout this process is the medial temporal lobe, and primarily the hippocampal region. Gender also has a considerable effect on volume deterioration of subcortical grey matter (GM) structures, such as the hippocampus. The influence of age×gender interaction on disproportionate GM volume changes might be mediated by hormonal effects on the brain. Hippocampal volume loss appears to become accelerated in the postmenopausal period. This decline might have significant influences on neuroplasticity in the CA1 region of the hippocampus highly vulnerable to pathological influences. Additionally, menopause has been associated with critical pathobiochemical changes involved in neurodegeneration. The micro- and macrostructural alterations and consequent functional deterioration of critical hippocampal regions might result in clinical cognitive impairment-especially if there already is a decline in the cognitive reserve capacity. Several lines of potential vulnerability factors appear to interact in the menopausal period eventually leading to cognitive decline, mild cognitive impairment, or Alzheimer's disease. This focused review aims to delineate the influence of unmodifiable risk factors of neurodegenerative processes, i.e., age and gender, on critical subcortical GM structures in the light of brain derived estrogen effects. The menopausal period appears to be of key importance for the risk of cognitive decline representing a time of special vulnerability for molecular, structural, and functional influences and offering only a narrow window for potential protective effects.

  17. Topographic organization of subcortical projections to the anterior thalamic nuclei in the rat.

    PubMed

    Shibata, H

    1992-09-01

    Subcortical projections to the anterior thalamic nuclei were studied in the rat, with special reference to projections from the mammillary nuclei, by retrograde and anterograde transport of wheat germ agglutinin conjugated to horseradish peroxidase. The medial mammillary nucleus (MM) projects predominantly ipsilaterally to the entire anterior thalamic nuclei, whereas the lateral mammillary nucleus projects bilaterally to the anterodorsal nucleus (AD) of the anterior thalamic nuclei. A topographic relationship was recognized between the MM and the anterior thalamic nuclei. The dorsal region of the pars mediana of the MM projects to the interanteromedial nucleus (IAM), whereas the ventral region projects to the rostral part of the anteromedial nucleus (AM). The dorsal and the ventral regions of the pars medialis project to the dorsomedial part of the AM at its caudal and rostral levels, respectively. The dorsomedial region of the pars lateralis projects to the ventral AM. The ventrolateral region of the pars lateralis projects to the ventral part of the anteroventral nucleus (AV) in such a manner that rostral cells project rostrally and caudal cells project caudally. The pars basalis projects predominantly ipsilaterally to the dorsolateral AV and bilaterally to the AD. The rostrolateral region of the pars posterior projects to the lateral AV, whereas the medial and the caudal regions of the pars posterior project to the dorsomedial AV. The rostrodorsal part of the nucleus reticularis thalami was found to project to the anterior thalamic nuclei; cells located rostrally in this part project to the IAM and AM, whereas cells located caudodorsally project to the AV and AD. The laterodorsal tegmental nucleus projects predominantly ipsilaterally to the AV, especially to its dorsolateral part. The present study demonstrates that subdivisions of the subcortical structures are connected to the subnuclei of the anterior thalamic nuclei, with a clear-cut topography arranged in

  18. Subcortical interactions between somatosensory stimuli of different modalities and their temporal profile.

    PubMed

    Costa, João; Valls-Solé, Josep; Valldeoriola, Francesc; Rumià, Jordi

    2008-09-01

    Interactions between inputs of different sensory modality occur along the sensory pathway, including the thalamus. However, the temporal profile of such interaction has not been fully studied. In eight patients who had been implanted an intrathalamic electrode for deep brain stimulation as symptomatic treatment of tremor, we investigated the interactions between mechanical taps and electrical nerve stimuli. Somatosensory evoked potentials (SEPs) were recorded from Erb's point, cervical spinal cord, nucleus ventrointermedialis of the thalamus, and parietal cortex. A handheld electronic reflex hammer was used to deliver a mechanical tap to the skin overlying the first dorsal interosseous muscle and to trigger an ipsilateral digital median nerve electrical stimulus time-locked to the mechanical tap with a variable delay of 0 to 50 ms. There were significant time-dependent interactions between the two sensory volleys at the subcortical level. Thalamic SEPs were decreased in amplitude at interstimulus intervals (ISIs) from 10 to 40 ms with maximum effect at 20 ms (-42.8 +/- 10.5%; P < 0.001). A similar decrease was also seen in the number and frequency of the high-frequency components of thalamic SEPs (-25 +/- 4%). A smaller reduction (-18.1 +/- 5.8%; P < 0.001) was present in upper cervical response at ISI = 20 ms. There were no changes in peripheral responses. Cortical SEPs were almost completely absent in some subjects at ISIs from 20 to 50 ms. There were no changes in SEP latencies. Our results indicate that significant time-dependent interactions between sensory volleys occur at the subcortical level. These observations provide further insight into the physiological mechanisms underlying afferent gating between sensory volleys of different modality.

  19. Sustained Cortical and Subcortical Measures of Auditory and Visual Plasticity following Short-Term Perceptual Learning.

    PubMed

    Lau, Bonnie K; Ruggles, Dorea R; Katyal, Sucharit; Engel, Stephen A; Oxenham, Andrew J

    2017-01-01

    Short-term training can lead to improvements in behavioral discrimination of auditory and visual stimuli, as well as enhanced EEG responses to those stimuli. In the auditory domain, fluency with tonal languages and musical training has been associated with long-term cortical and subcortical plasticity, but less is known about the effects of shorter-term training. This study combined electroencephalography (EEG) and behavioral measures to investigate short-term learning and neural plasticity in both auditory and visual domains. Forty adult participants were divided into four groups. Three groups trained on one of three tasks, involving discrimination of auditory fundamental frequency (F0), auditory amplitude modulation rate (AM), or visual orientation (VIS). The fourth (control) group received no training. Pre- and post-training tests, as well as retention tests 30 days after training, involved behavioral discrimination thresholds, steady-state visually evoked potentials (SSVEP) to the flicker frequencies of visual stimuli, and auditory envelope-following responses simultaneously evoked and measured in response to rapid stimulus F0 (EFR), thought to reflect subcortical generators, and slow amplitude modulation (ASSR), thought to reflect cortical generators. Enhancement of the ASSR was observed in both auditory-trained groups, not specific to the AM-trained group, whereas enhancement of the SSVEP was found only in the visually-trained group. No evidence was found for changes in the EFR. The results suggest that some aspects of neural plasticity can develop rapidly and may generalize across tasks but not across modalities. Behaviorally, the pattern of learning was complex, with significant cross-task and cross-modal learning effects.

  20. A Bayesian model of shape and appearance for subcortical brain segmentation.

    PubMed

    Patenaude, Brian; Smith, Stephen M; Kennedy, David N; Jenkinson, Mark

    2011-06-01

    Automatic segmentation of subcortical structures in human brain MR images is an important but difficult task due to poor and variable intensity contrast. Clear, well-defined intensity features are absent in many places along typical structure boundaries and so extra information is required to achieve successful segmentation. A method is proposed here that uses manually labelled image data to provide anatomical training information. It utilises the principles of the Active Shape and Appearance Models but places them within a Bayesian framework, allowing probabilistic relationships between shape and intensity to be fully exploited. The model is trained for 15 different subcortical structures using 336 manually-labelled T1-weighted MR images. Using the Bayesian approach, conditional probabilities can be calculated easily and efficiently, avoiding technical problems of ill-conditioned covariance matrices, even with weak priors, and eliminating the need for fitting extra empirical scaling parameters, as is required in standard Active Appearance Models. Furthermore, differences in boundary vertex locations provide a direct, purely local measure of geometric change in structure between groups that, unlike voxel-based morphometry, is not dependent on tissue classification methods or arbitrary smoothing. In this paper the fully-automated segmentation method is presented and assessed both quantitatively, using Leave-One-Out testing on the 336 training images, and qualitatively, using an independent clinical dataset involving Alzheimer's disease. Median Dice overlaps between 0.7 and 0.9 are obtained with this method, which is comparable or better than other automated methods. An implementation of this method, called FIRST, is currently distributed with the freely-available FSL package.

  1. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) associated with a novel C82R mutation in the NOTCH3 gene.

    PubMed

    Zea-Sevilla, M Ascensión; Bermejo-Velasco, Pedro; Serrano-Heranz, Regino; Calero, Miguel

    2015-01-01

    Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare inherited cerebrovascular disease associated with mutations in the NOTCH3 gene on chromosome 19, and represents the most common hereditary stroke disorder. We describe a pedigree, which suffered the classical clinical CADASIL pattern of migraine headaches, recurrent subcortical infarcts, and subcortical dementia, associated with a previously undescribed missense mutation (c.[244T>C], p.[C82R]) in NOTCH3. This new mutation extends the list of known pathogenic mutations responsible for CADASIL, which are associated with an odd number of cysteine residues within any of the epidermal growth factor-like repeats of Notch3 receptor protein.

  2. Increased Functional Connectivity Between Subcortical and Cortical Resting-State Networks in Autism Spectrum Disorder

    PubMed Central

    Cerliani, Leonardo; Mennes, Maarten; Thomas, Rajat M.; Di Martino, Adriana; Thioux, Marc; Keysers, Christian

    2016-01-01

    Importance Individuals with autism spectrum disorder (ASD) exhibit severe difficulties in social interaction, motor coordination, behavioral flexibility, and atypical sensory processing, with considerable interindividual variability. This heterogeneous set of symptoms recently led to investigating the presence of abnormalities in the interaction across large-scale brain networks. To date, studies have focused either on constrained sets of brain regions or whole-brain analysis, rather than focusing on the interaction between brain networks. Objectives To compare the intrinsic functional connectivity between brain networks in a large sample of individuals with ASD and typically developing control subjects and to estimate to what extent group differences would predict autistic traits and reflect different developmental trajectories. Design, Setting, and Participants We studied 166 male individuals (mean age, 17.6 years; age range, 7-50 years) diagnosed as having DSM-IV-TR autism or Asperger syndrome and 193 typical developing male individuals (mean age, 16.9 years; age range, 6.5-39.4 years) using resting-state functional magnetic resonance imaging (MRI). Participants were matched for age, IQ, head motion, and eye status (open or closed) in the MRI scanner. We analyzed data from the Autism Brain Imaging Data Exchange (ABIDE), an aggregated MRI data set from 17 centers, made public in August 2012. Main Outcomes and Measures We estimated correlations between time courses of brain networks extracted using a data-driven method (independent component analysis). Subsequently, we associated estimates of interaction strength between networks with age and autistic traits indexed by the Social Responsiveness Scale. Results Relative to typically developing control participants, individuals with ASD showed increased functional connectivity between primary sensory networks and subcortical networks (thalamus and basal ganglia) (all t ≥ 3.13, P < .001 corrected). The strength of

  3. Autonomic responses to exercise: cortical and subcortical responses during post-exercise ischaemia and muscle pain.

    PubMed

    Macefield, Vaughan G; Henderson, Luke A

    2015-03-01

    Sustained isometric contraction of skeletal muscle causes an increase in blood pressure, due to an increase in cardiac output and an increase in total peripheral resistance-brought about by an increase in sympathetically-mediated vasoconstriction. Both central command and reflex inputs from metaboreceptors in the contracting muscles have been shown to contribute to this sympathetically mediated increase in blood pressure. Occluding the blood supply and trapping the metabolites in the contracted muscle (post-exercise ischaemia) has shown that, while heart rate returns to baseline following exercise, the increase in MSNA and blood pressure persists in the absence of central command-sustained by peripheral inputs. Post-exercise ischaemia activates group III and IV muscle afferents, which are also activated during noxious stimulation. Indeed, post-exercise ischaemia is painful, so what is the role of pain in the increase in blood pressure? Intramuscular injection of hypertonic saline causes a deep dull ache, not unlike that produced by post-exercise ischaemia, and we have shown that this can cause a sustained increase in MSNA and blood pressure. We have used functional Magnetic Resonance Imaging (fMRI) of the brain to identify the cortical and subcortical sites involved in the sensory processing of muscle pain, and in the generation of the autonomic responses to muscle pain, produced either by post-exercise ischaemia or intramuscular injection of hypertonic saline. During static hand-grip exercise there were parallel increases in signal intensity in the contralateral primary motor cortex, deep cerebellar nuclei and cerebellar cortex that ceased at the end of the exercise, reflecting the start and end of central command. Progressive increases during the contraction phase occurred in the contralateral insula, as well as the contralateral primary somatosensory cortex, and continued during the period of post-exercise ischaemia. Decreases in signal intensity occurred in the

  4. Right Frontoinsular Cortex and Subcortical Activity to Infant Cry Is Associated with Maternal Mental State Talk

    PubMed Central

    Phillips, Mary L.; Swain, James E.; Moses-Kolko, Eydie L.

    2015-01-01

    The study objective was to examine neural correlates of a specific component of human caregiving: maternal mental state talk, reflecting a mother's proclivity to attribute mental states and intentionality to her infant. Using a potent, ecologically relevant stimulus of infant cry during fMRI, we tested hypotheses that postpartum neural response to the cry of “own” versus a standard “other” infant in the right frontoinsular cortex (RFIC) and subcortical limbic network would be associated with independent observations of maternal mental state talk. The sample comprised 76 urban-living, low socioeconomic mothers (82% African American) and their 4-month-old infants. Before the fMRI scan, mothers were filmed in face-to-face interaction with their infant, and maternal behaviors were coded by trained researchers unaware of all other information about the participants. The results showed higher functional activity in the RFIC to own versus other infant cry at the group level. In addition, RFIC and bilateral subcortical neural activity (e.g., thalamus, amygdala, hippocampus, putamen) was associated positively with maternal mental state talk but not with more global aspects of observed caregiving. These findings held when accounting for perceptual and contextual covariates, such as maternal felt distress, urge to help, depression severity, and recognition of own infant cry. Our results highlight the need to focus on specific components of caregiving to advance understanding of the maternal brain. Future work will examine the predictive utility of this neural marker for mother–child function. SIGNIFICANCE STATEMENT The current study advances extant literature examining the neural underpinning of early parenting behavior. The findings highlight the special functional importance of the right frontoinsular cortex–thalamic–limbic network in a mother's proclivity to engage in mental state talk with her preverbal infant, a circumscribed aspect of maternal caregiving

  5. Vector affinity and diversity of Geosmithia fungi living on subcortical insects inhabiting Pinaceae species in central and northeastern Europe.

    PubMed

    Kolařík, Miroslav; Jankowiak, Robert

    2013-10-01

    Fungi from the genus Geosmithia (Ascomycota: Hypocreales) are associated with bark beetles (Coleoptera: Scolytinae), though little is known about ecology, diversity, and distribution of these fungi across beetle and its host tree species. This study surveyed the diversity, distribution and vector affinity of Geosmithia isolated from subcortical insects that colonized trees from the family Pinaceae in Central and Northeastern Europe. Twelve Geosmithia species were isolated from 85 plant samples associated with 23 subcortical insect species (including 14 bark beetle species). Geosmithia community composition was similar across different localities and vector species; although the fungal communities associated with insects that colonized Pinus differed from that colonizing other tree species (Abies, Larix, and Picea). Ten Geosmithia species from four independent phylogenetic lineages were not reported previously from vectors feeding on other plant families and seem to be restricted to the vectors from Pinaceae only. We conclude that presence of such substrate specificity suggests a long and stable association between Geosmithia and bark beetles.

  6. Genetic influences on schizophrenia and subcortical brain volumes: large-scale proof-of-concept and roadmap for future studies

    PubMed Central

    Anttila, Verneri; Hibar, Derrek P; van Hulzen, Kimm J E; Arias-Vasquez, Alejandro; Smoller, Jordan W; Nichols, Thomas E; Neale, Michael C; McIntosh, Andrew M; Lee, Phil; McMahon, Francis J; Meyer-Lindenberg, Andreas; Mattheisen, Manuel; Andreassen, Ole A; Gruber, Oliver; Sachdev, Perminder S; Roiz-Santiañez, Roberto; Saykin, Andrew J; Ehrlich, Stefan; Mather, Karen A; Turner, Jessica A; Schwarz, Emanuel; Thalamuthu, Anbupalam; Shugart, Yin Yao; Ho, Yvonne YW; Martin, Nicholas G; Wright, Margaret J

    2016-01-01

    Schizophrenia is a devastating psychiatric illness with high heritability. Brain structure and function differ, on average, between schizophrenia cases and healthy individuals. As common genetic associations are emerging for both schizophrenia and brain imaging phenotypes, we can now use genome-wide data to investigate genetic overlap. Here we integrated results from common variant studies of schizophrenia (33,636 cases, 43,008 controls) and volumes of several (mainly subcortical) brain structures (11,840 subjects). We did not find evidence of genetic overlap between schizophrenia risk and subcortical volume measures either at the level of common variant genetic architecture or for single genetic markers. The current study provides proof-of-concept (albeit based on a limited set of structural brain measures), and defines a roadmap for future studies investigating the genetic covariance between structural/functional brain phenotypes and risk for psychiatric disorders. PMID:26854805

  7. Medial Demons Registration Localizes The Degree of Genetic Influence Over Subcortical Shape Variability: An N= 1480 Meta-Analysis

    PubMed Central

    Gutman, Boris A.; Jahanshad, Neda; Ching, Christopher R.K.; Wang, Yalin; Kochunov, Peter V.; Nichols, Thomas E.; Thompson, Paul M.

    2015-01-01

    We present a multi-cohort shape heritability study, extending the fast spherical demons registration to subcortical shapes via medial modeling. A multi-channel demons registration based on vector spherical harmonics is applied to medial and curvature features, while controlling for metric distortion. We registered and compared seven subcortical structures of 1480 twins and siblings from the Queensland Twin Imaging Study and Human Connectome Project: Thalamus, Caudate, Putamen, Pallidum, Hippocampus, Amygdala, and Nucleus Accumbens. Radial distance and tensor-based morphometry (TBM) features were found to be highly heritable throughout the entire basal ganglia and limbic system. Surface maps reveal subtle variation in heritability across functionally distinct parts of each structure. Medial Demons reveals more significantly heritable regions than two previously described surface registration methods. This approach may help to prioritize features and measures for genome-wide association studies. PMID:26413211

  8. Influence of education on subcortical hyperintensities and global cognitive status in vascular dementia.

    PubMed

    Lane, Elizabeth M; Paul, Robert H; Moser, David J; Fletcher, Thomas D; Cohen, Ronald A

    2011-05-01

    Subcortical hyperintensities (SH) on neuroimaging are a prominent feature of vascular dementia (VaD) and SH severity correlates with cognitive impairment in this population. Previous studies demonstrated that SH burden accounts for a degree of the cognitive burden among VaD patients, although it remains unclear if individual factors such as cognitive reserve influence cognitive status in VaD. To address this issue, we examined 36 individuals diagnosed with probable VaD (age = 77.56; education = 12). All individuals underwent MMSE evaluations and MRI brain scans. We predicted that individuals with higher educational attainment would exhibit less cognitive difficulty despite similar levels of SH volume, compared to individuals with less educational attainment. A regression analysis revealed that greater SH volume was associated with lower scores on the MMSE. Additionally, education moderated the relationship between SH volume and MMSE score, demonstrating that individuals with higher education had higher scores on the MMSE despite similar degrees of SH burden. These results suggest that educational attainment buffers the deleterious effects of SH burden on cognitive status among VaD patients.

  9. It’s All in the Eyes: Subcortical and Cortical Activation during Grotesqueness Perception in Autism

    PubMed Central

    Zürcher, Nicole R.; Donnelly, Nick; Rogier, Ophélie; Russo, Britt; Hippolyte, Loyse; Hadwin, Julie; Lemonnier, Eric; Hadjikhani, Nouchine

    2013-01-01

    Atypical face processing plays a key role in social interaction difficulties encountered by individuals with autism. In the current fMRI study, the Thatcher illusion was used to investigate several aspects of face processing in 20 young adults with high-functioning autism spectrum disorder (ASD) and 20 matched neurotypical controls. “Thatcherized” stimuli were modified at either the eyes or the mouth and participants discriminated between pairs of faces while cued to attend to either of these features in upright and inverted orientation. Behavioral data confirmed sensitivity to the illusion and intact configural processing in ASD. Directing attention towards the eyes vs. the mouth in upright faces in ASD led to (1) improved discrimination accuracy; (2) increased activation in areas involved in social and emotional processing; (3) increased activation in subcortical face-processing areas. Our findings show that when explicitly cued to attend to the eyes, activation of cortical areas involved in face processing, including its social and emotional aspects, can be enhanced in autism. This suggests that impairments in face processing in autism may be caused by a deficit in social attention, and that giving specific cues to attend to the eye-region when performing behavioral therapies aimed at improving social skills may result in a better outcome. PMID:23342130

  10. Tract-Specific Correlates of Neuropsychological Deficits in Patients with Subcortical Vascular Cognitive Impairment.

    PubMed

    Jung, Na-Yeon; Han, Cheol E; Kim, Hee Jin; Yoo, Sang Wook; Kim, Hee-Jong; Kim, Eun-Joo; Na, Duk L; Lockhart, Samuel N; Jagust, William J; Seong, Joon-Kyung; Seo, Sang Won

    2016-01-01

    The white matter tract-specific correlates of neuropsychological deficits are not fully established in patients with subcortical vascular cognitive impairment (SVCI), where white matter tract damage may be a critical factor in cognitive impairment. The purpose of this study is to investigate the tract-specific correlates of neuropsychological deficits in SVCI patients using tract-specific statistical analysis (TSSA). We prospectively recruited 114 SVCI patients, and 55 age-, gender-, and education-matched individuals with normal cognition (NC). All participants underwent diffusion weighted imaging and neuropsychological testing. We classified tractography results into fourteen major fiber tracts and analyzed group comparison and correlation with cognitive impairments. Relative to NC subjects, SVCI patients showed decreased fractional anisotropy values in bilateral anterior-thalamic radiation, cingulum, superior-longitudinal fasciculus, uncinate fasciculus, corticospinal tract, and left inferior-longitudinal fasciculus. Focal disruptions in specific tracts were associated with specific cognitive impairments. Our findings suggest that disconnection of specific white matter tracts, especially those neighboring and providing connections between gray matter regions important to certain cognitive functions, may contribute to specific cognitive impairments in SVCI.

  11. A mu-delta opioid receptor brain atlas reveals neuronal co-occurrence in subcortical networks.

    PubMed

    Erbs, Eric; Faget, Lauren; Scherrer, Gregory; Matifas, Audrey; Filliol, Dominique; Vonesch, Jean-Luc; Koch, Marc; Kessler, Pascal; Hentsch, Didier; Birling, Marie-Christine; Koutsourakis, Manoussos; Vasseur, Laurent; Veinante, Pierre; Kieffer, Brigitte L; Massotte, Dominique

    2015-03-01

    Opioid receptors are G protein-coupled receptors (GPCRs) that modulate brain function at all levels of neural integration, including autonomic, sensory, emotional and cognitive processing. Mu (MOR) and delta (DOR) opioid receptors functionally interact in vivo, but whether interactions occur at circuitry, cellular or molecular levels remains unsolved. To challenge the hypothesis of MOR/DOR heteromerization in the brain, we generated redMOR/greenDOR double knock-in mice and report dual receptor mapping throughout the nervous system. Data are organized as an interactive database offering an opioid receptor atlas with concomitant MOR/DOR visualization at subcellular resolution, accessible online. We also provide co-immunoprecipitation-based evidence for receptor heteromerization in these mice. In the forebrain, MOR and DOR are mainly detected in separate neurons, suggesting system-level interactions in high-order processing. In contrast, neuronal co-localization is detected in subcortical networks essential for survival involved in eating and sexual behaviors or perception and response to aversive stimuli. In addition, potential MOR/DOR intracellular interactions within the nociceptive pathway offer novel therapeutic perspectives.

  12. Multimodality multidimensional image analysis of cortical and subcortical plasticity in the rat brain.

    PubMed

    Goldszal, A F; Tretiak, O J; Liu, D D; Hand, P J

    1996-01-01

    In this work, we developed and implemented a multimodality multidimensional imaging system which is capable of generating and displaying anatomical and functional images of selected structures and processes within a vertebrate's central nervous system (CNS). The functional images are generated from [14C]-2-deoxy-D-glucose (2DG) autoradiography whereas the anatomic images are derived from cytochrome oxidase (CO) histochemistry. This multi-modality imaging system has been used to study mechanisms underlying information processing in the rat brain. We have applied this technique to visualize and measure the plasticity (deformation) observed in the rat's whisker system due to neonatal lesioning of selected peripheral sensory organs. Application of this imaging system revealed detailed information about the shape, size, and directionality of selected cortical and subcortical structures. Previous 2-D imaging techniques were unable to deliver such holistic information. Another important issue addressed in this work is related to image registration problems. We developed an image registration technique which employs extrinsic fiduciary marks for alignment and is capable of registering images with subpixel accuracy. It uses the information from all available fiduciary marks to promote alignment of the sections and to avoid propagation of errors across a serial data set.

  13. Training conquers multitasking costs by dividing task representations in the frontoparietal-subcortical system.

    PubMed

    Garner, K G; Dux, Paul E

    2015-11-17

    Negotiating the information-rich sensory world often requires the concurrent management of multiple tasks. Despite this requirement, humans are thought to be poor at multitasking because of the processing limitations of frontoparietal and subcortical (FP-SC) brain regions. Although training is known to improve multitasking performance, it is unknown how the FP-SC system functionally changes to support improved multitasking. To address this question, we characterized the FP-SC changes that predict training outcomes using an individual differences approach. Participants (n = 100) performed single and multiple tasks in pre- and posttraining magnetic resonance imaging (fMRI) sessions interspersed by either a multitasking or an active-control training regimen. Multivoxel pattern analyses (MVPA) revealed that training induced multitasking improvements were predicted by divergence in the FP-SC blood oxygen level-dependent (BOLD) response patterns to the trained tasks. Importantly, this finding was only observed for participants who completed training on the component (single) tasks and their combination (multitask) and not for the control group. Therefore, the FP-SC system supports multitasking behavior by segregating constituent task representations.

  14. [Spectral characteristics of the bioelectrical activity of the cerebral cortex upon electric stimulation of subcortical structures].

    PubMed

    Ianson, Z A; Markin, V P

    1976-01-01

    A spectral-correlation analysis of electrical activity of the rabbit cerebral cortex was made with the use of Dnieper computer, after electrical stimulation (100-250 c/s) of the midbrain reticular formation, the thalamic nonspecific formations (midline nuclei) and different nuclei of the posterior part of the hypothalamic area (ventromedial and posterior hypothalamic nuclei and the lateral field). The background spectrograms were characterized by a high variability; their frequencies ranged from 0,5 to 12 c/s. Under the influence of the electrical stimulation of the indicated formations, a well-pronounced, dominating peak appeared in the spectrograms of the cortical EEG, in the band from 4 to 7 c/s, and the similarity of biopotentials in this rhythm increased. The experimental data show that enhancement of spatial synchronization of the cortical biopotentials under conditions of electrical stimulation of the indicated subcortical formations is based on increased rhythmic oscillations within the theta-band and on a greater coherence in this range.

  15. Neuroimaging of major depression in Parkinson's disease: Cortical thickness, cortical and subcortical volume, and spectroscopy findings.

    PubMed

    Chagas, Marcos Hortes N; Tumas, Vitor; Pena-Pereira, Márcio A; Machado-de-Sousa, João Paulo; Carlos Dos Santos, Antonio; Sanches, Rafael Faria; Hallak, Jaime E C; Crippa, José Alexandre S

    2017-02-13

    Depression is the most common psychiatric disorder in Parkinson's disease (PD). The aim of this study was to compare PD patients with current Major Depressive Disorder (MDD), lifetime MDD, and no MDD using three neuroimaging techniques. A total of 43 PD patients were selected and divided into three groups: (i) current MDD (n = 15), (ii) previous MDD without current MDD (n = 10); and (iii) control group (no current or lifetime MDD; n = 18). All participants underwent magnetic resonance imaging to evaluate cortical thickness, cortical and subcortical volume, and spectroscopy in the bilateral putamen and cingulate cortex. Volumetric analysis showed volume decreases in frontal and temporal areas, bilateral amygdala, and left cerebellar white matter in the lifetime MDD group compared to the control group. Furthermore, the volumes of the anterior cingulate cortex, right amygdala, and left cerebellar white matter were smaller in the group with current MDD compared to the control group. Regarding cortical thickness, the left rostral anterior cingulate gyrus of the group with previous MDD was thinner compared to the control group. There was a weak negative correlation between the NAA/Cre ratio in the right putamen and depressive symptoms. The results suggested current and lifetime MDD have a negative impact on the neurodegenerative process of PD, with decreased volume and/or reduction of cortical thickness in temporal and frontal areas, anterior cingulate cortex, amygdala, and cerebellar white matter.

  16. In Vivo Voltage-Sensitive Dye Imaging of Subcortical Brain Function.

    PubMed

    Tang, Qinggong; Tsytsarev, Vassiliy; Liang, Chia-Pin; Akkentli, Fatih; Erzurumlu, Reha S; Chen, Yu

    2015-11-27

    The whisker system of rodents is an excellent model to study peripherally evoked neural activity in the brain. Discrete neural modules represent each whisker in the somatosensory cortex ("barrels"), thalamus ("barreloids"), and brain stem ("barrelettes"). Stimulation of a single whisker evokes neural activity sequentially in its corresponding barrelette, barreloid, and barrel. Conventional optical imaging of functional activation in the brain is limited to surface structures such as the cerebral cortex. To access subcortical structures and image sensory-evoked neural activity, we designed a needle-based optical system using gradient-index (GRIN) rod lens. We performed voltage-sensitive dye imaging (VSDi) with GRIN rod lens to visualize neural activity evoked in the thalamic barreloids by deflection of whiskers in vivo. We stimulated several whiskers together to determine the sensitivity of our approach in differentiating between different barreloid responses. We also carried out stimulation of different whiskers at different times. Finally, we used muscimol in the barrel cortex to silence the corticothalamic inputs while imaging in the thalamus. Our results show that it is possible to obtain functional maps of the sensory periphery in deep brain structures such as the thalamic barreloids. Our approach can be broadly applicable to functional imaging of other core brain structures.

  17. Blood and CSF biomarkers in brain subcortical ischemic vascular disease: Involved pathways and clinical applicability

    PubMed Central

    Vilar-Bergua, A; Riba-Llena, I; Nafría, C; Bustamante, A; Llombart, V; Delgado, P

    2016-01-01

    Vascular dementia is the second most common type of dementia after Alzheimer’s disease (AD). Subcortical ischemic vascular disease refers to a form of vascular cognitive impairment characterized by the presence of diffuse white matter hyperintensities (WMHs) and multiple lacunar infarcts. These neuroimaging findings are mainly caused by cerebral small-vessel disease (cSVD) and relate to aging and cognitive impairment, but they can also be silent and highly prevalent in otherwise healthy individuals. We aimed to review studies on blood and cerebrospinal fluid (CSF) markers related to the presence of WMHs and lacunar infarcts that have been conducted in the past in large population-based studies and in high-risk selected patients (such as those with vascular risk factors, vascular cognitive impairment, or AD). Relevant associations with the presence and progression of cSVD have been described in the blood for markers related to inflammatory processes, endothelial damage and coagulation/fibrinolysis processes, etc. Also, different combinations of CSF markers might help to differentiate between etiologic types of dementia. In the future, to translate these findings into clinical practice and use biomarkers to early diagnosis and monitoring vascular cognitive impairment would require the replication of candidate markers in large-scale, multicenter, and prospectively designed studies. PMID:25899297

  18. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) - literature review apropos an autopsy case.

    PubMed

    Wesołowski, Wojciech; Dziewulska, Dorota; Koziarska, Malwina; Iżycka-Świeszewska, Ewa

    2015-09-01

    Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a non-atherosclerotic, non-amyloid cerebral angiopathy involving small arteries and arterioles. This entity presents vascular changes in the form of smooth muscle degeneration with swollen myocytes and PAS-positive granular deposits, together with vascular fibrosis and hyalinization. In parallel, diffuse white matter destruction with infarcts, tissue rarefaction, spongiosis, lacunes and demyelination are characteristic. Ultrastructurally, vascular granular osmiophilic material (GOM) is pathognomonic for this hereditary disease caused by NOTCH3 mutation. We diagnosed CADASIL in the autopsy examination of a 53-year-old woman with a 9-year history of a progressive neurological disease with complex motor and cognitive deficits, accompanied by non-specific diffuse white matter changes on neuroimaging. Despite several multicentre hospitalizations, the precise diagnosis was not established until the post-mortem examination of the brain was made. CADASIL is a rare entity, but it should be considered by a pathologist in a differential diagnosis of vascular diseases of the brain, especially in cases with atypical clinical presentation and familial history. The prompt diagnosis depends on the quality of the brain autopsy and proper sampling. The post mortem examination, where “Morituri vivos docent”, is still significant.

  19. In Vivo Voltage-Sensitive Dye Imaging of Subcortical Brain Function

    NASA Astrophysics Data System (ADS)

    Tang, Qinggong; Tsytsarev, Vassiliy; Liang, Chia-Pin; Akkentli, Fatih; Erzurumlu, Reha S.; Chen, Yu

    2015-11-01

    The whisker system of rodents is an excellent model to study peripherally evoked neural activity in the brain. Discrete neural modules represent each whisker in the somatosensory cortex (“barrels”), thalamus (“barreloids”), and brain stem (“barrelettes”). Stimulation of a single whisker evokes neural activity sequentially in its corresponding barrelette, barreloid, and barrel. Conventional optical imaging of functional activation in the brain is limited to surface structures such as the cerebral cortex. To access subcortical structures and image sensory-evoked neural activity, we designed a needle-based optical system using gradient-index (GRIN) rod lens. We performed voltage-sensitive dye imaging (VSDi) with GRIN rod lens to visualize neural activity evoked in the thalamic barreloids by deflection of whiskers in vivo. We stimulated several whiskers together to determine the sensitivity of our approach in differentiating between different barreloid responses. We also carried out stimulation of different whiskers at different times. Finally, we used muscimol in the barrel cortex to silence the corticothalamic inputs while imaging in the thalamus. Our results show that it is possible to obtain functional maps of the sensory periphery in deep brain structures such as the thalamic barreloids. Our approach can be broadly applicable to functional imaging of other core brain structures.

  20. Training conquers multitasking costs by dividing task representations in the frontoparietal-subcortical system

    PubMed Central

    Garner, K. G.; Dux, Paul E.

    2015-01-01

    Negotiating the information-rich sensory world often requires the concurrent management of multiple tasks. Despite this requirement, humans are thought to be poor at multitasking because of the processing limitations of frontoparietal and subcortical (FP-SC) brain regions. Although training is known to improve multitasking performance, it is unknown how the FP-SC system functionally changes to support improved multitasking. To address this question, we characterized the FP-SC changes that predict training outcomes using an individual differences approach. Participants (n = 100) performed single and multiple tasks in pre- and posttraining magnetic resonance imaging (fMRI) sessions interspersed by either a multitasking or an active-control training regimen. Multivoxel pattern analyses (MVPA) revealed that training induced multitasking improvements were predicted by divergence in the FP-SC blood oxygen level-dependent (BOLD) response patterns to the trained tasks. Importantly, this finding was only observed for participants who completed training on the component (single) tasks and their combination (multitask) and not for the control group. Therefore, the FP-SC system supports multitasking behavior by segregating constituent task representations. PMID:26460014

  1. Hippocampal subfield volumetry in patients with subcortical vascular mild cognitive impairment

    PubMed Central

    Li, Xinwei; Li, Deyu; Li, Qiongling; Li, Yuxia; Li, Kuncheng; Li, Shuyu; Han, Ying

    2016-01-01

    Memory impairment is a typical characteristic of patients with subcortical vascular mild cognitive impairment (svMCI) or with amnestic mild cognitive impairment (aMCI). The hippocampus, which plays an important role in the consolidation of information from short-term memory to long-term memory, is a heterogeneous structure that consists of several anatomically and functionally distinct subfields. However, whether distinct hippocampal subfields are differentially and selectively affected by svMCI pathology and whether these abnormal changes in hippocampal subfields are different between svMCI and aMCI patients are largely unknown. A total of 26 svMCI patients, 26 aMCI patients and 26 healthy controls matched according to age, gender and years of education were enrolled in this study. We utilized an automated hippocampal subfield segmentation method provided by FreeSurfer to estimate the volume of several hippocampal subfields, including the cornu ammonis (CA) areas, the dentate gyrus (DG), the subiculum and the presubiculum. Compared with controls, the left subiculum and presubiculum and the right CA4/DG displayed significant atrophy in patients with svMCI. Interestingly, we also found significant differences in the volume of the right CA1 between the svMCI and aMCI groups. Taken together, our results reveal region-specific vulnerability of hippocampal subfields to svMCI pathology and identify distinct hippocampal subfield atrophy patterns between svMCI and aMCI patients. PMID:26876151

  2. In vivo imaging reveals that pregabalin inhibits cortical spreading depression and propagation to subcortical brain structures

    PubMed Central

    Cain, Stuart M.; Bohnet, Barry; LeDue, Jeffrey; Yung, Andrew C.; Garcia, Esperanza; Tyson, John R.; Alles, Sascha R. A.; Han, Huili; van den Maagdenberg, Arn M. J. M.; Kozlowski, Piotr; MacVicar, Brian A.; Snutch, Terrance P.

    2017-01-01

    Migraine is characterized by severe headaches that can be preceded by an aura likely caused by cortical spreading depression (SD). The antiepileptic pregabalin (Lyrica) shows clinical promise for migraine therapy, although its efficacy and mechanism of action are unclear. As detected by diffusion-weighted MRI (DW-MRI) in wild-type (WT) mice, the acute systemic administration of pregabalin increased the threshold for SD initiation in vivo. In familial hemiplegic migraine type 1 mutant mice expressing human mutations (R192Q and S218L) in the CaV2.1 (P/Q-type) calcium channel subunit, pregabalin slowed the speed of SD propagation in vivo. Acute systemic administration of pregabalin in vivo also selectively prevented the migration of SD into subcortical striatal and hippocampal regions in the R192Q strain that exhibits a milder phenotype and gain of CaV2.1 channel function. At the cellular level, pregabalin inhibited glutamatergic synaptic transmission differentially in WT, R192Q, and S218L mice. The study describes a DW-MRI analysis method for tracking the progression of SD and provides support and a mechanism of action for pregabalin as a possible effective therapy in the treatment of migraine. PMID:28223480

  3. Cortical thinning in subcortical vascular dementia with negative 11C-PiB PET.

    PubMed

    Kim, Chi Hun; Seo, Sang Won; Kim, Geon Ha; Shin, Ji Soo; Cho, Hanna; Noh, Young; Kim, Suk-Hui; Kim, Min Ji; Jeon, Seun; Yoon, Uicheul; Lee, Jong-Min; Oh, Seung Jun; Kim, Jae Seung; Kim, Sung Tae; Lee, Jae-Hong; Na, Duk L

    2012-01-01

    To determine the existence of cortical thinning in subcortical vascular dementia (SVaD) with a negative 11C-Pittsburgh compound B (PiB) positron emission tomography scan and to compare the topography of cortical thinning between PiB-negative SVaD and Alzheimer's disease (AD), we enrolled 24 patients with PiB(-) SVaD, 81 clinically probable AD individuals, and 72 normal cognitive controls. Compared with controls, cortical thinning in PiB(-) SVaD was most profound in the perisylvian area, medial prefrontal area, and posterior cingulate gyri, while the precuneus and medial temporal lobes were relatively spared. When the cortical thickness of AD and PiB(-) SVaD were directly compared, PiB(-) SVaD demonstrated significant cortical thinning in the bilateral inferior frontal, superior temporal gyri, and right medial frontal and orbitofrontal lobes, while AD showed significant cortical thinning in the right medial temporal region. SVaD without amyloid burden may lead to substantial cortical atrophy. Moreover, characteristic topography of cortical thinning in PiB(-) SVaD suggests different mechanisms of cortical thinning in PiB(-) SVaD and AD.

  4. Decreased centrality of subcortical regions during the transition to adolescence: a functional connectivity study.

    PubMed

    Sato, João Ricardo; Salum, Giovanni Abrahão; Gadelha, Ary; Vieira, Gilson; Zugman, André; Picon, Felipe Almeida; Pan, Pedro Mario; Hoexter, Marcelo Queiroz; Anés, Mauricio; Moura, Luciana Monteiro; Del'Aquilla, Marco Antonio Gomes; Crossley, Nicolas; Amaro Junior, Edson; Mcguire, Philip; Lacerda, Acioly L T; Rohde, Luis Augusto; Miguel, Euripedes Constantino; Jackowski, Andrea Parolin; Bressan, Rodrigo Affonseca

    2015-01-01

    Investigations of brain maturation processes are a key step to understand the cognitive and emotional changes of adolescence. Although structural imaging findings have delineated clear brain developmental trajectories for typically developing individuals, less is known about the functional changes of this sensitive development period. Developmental changes, such as abstract thought, complex reasoning, and emotional and inhibitory control, have been associated with more prominent cortical control. The aim of this study is to assess brain networks connectivity changes in a large sample of 7- to 15-year-old subjects, testing the hypothesis that cortical regions will present an increasing relevance in commanding the global network. Functional magnetic resonance imaging (fMRI) data were collected in a sample of 447 typically developing children from a Brazilian community sample who were submitted to a resting state acquisition protocol. The fMRI data were used to build a functional weighted graph from which eigenvector centrality (EVC) was extracted. For each brain region (a node of the graph), the age-dependent effect on EVC was statistically tested and the developmental trajectories were estimated using polynomial functions. Our findings show that angular gyrus become more central during this maturation period, while the caudate; cerebellar tonsils, pyramis, thalamus; fusiform, parahippocampal and inferior semilunar lobe become less central. In conclusion, we report a novel finding of an increasing centrality of the angular gyrus during the transition to adolescence, with a decreasing centrality of many subcortical and cerebellar regions.

  5. The neural correlates of motor intentional disorders in patients with subcortical vascular cognitive impairment.

    PubMed

    Kim, Geon Ha; Seo, Sang Won; Jung, Kihyo; Kwon, Oh-Hun; Kwon, Hunki; Kim, Jong Hun; Roh, Jee Hoon; Kim, Min-Jeong; Lee, Byung Hwa; Yoon, Doo Sang; Hwang, Jung Won; Lee, Jong Min; Jeong, Jee Hyang; You, Heecheon; Heilman, Kenneth M; Na, Duk L

    2016-01-01

    Subcortical vascular cognitive impairment (SVCI) refers to cognitive impairment associated with small vessel disease. Motor intentional disorders (MID) have been reported in patients with SVCI. However, there are no studies exploring the neuroanatomical regions related to MID in SVCI patients. The aim of this study, therefore, was to investigate the neural correlates of MID in SVCI patients. Thirty-one patients with SVCI as well as 10 healthy match control participants were included. A "Pinch-Grip" apparatus was used to quantify the force control capabilities of the index finger in four different movement phases including initiation, development, maintenance, and termination. All participants underwent magnetic resonance imaging (MRI). Topographical cortical areas and white matter tracts correlated with the performances of the four different movement phases were assessed by the surface-based morphometry and tract-based spatial statistics analyses. Poorer performance in the maintenance task was related to cortical thinning in bilateral dorsolateral prefrontal, orbitofrontal and parietal cortices, while poorer performance in the termination task was associated with the disruption of fronto-parietal cortical areas as well as the white matter tracts including splenium and association fibers such as superior longitudinal fasciculus. Our study demonstrates that cortical areas and underlying white matter tracts associated with fronto-parietal attentional system play an important role in motor impersistence and perseveration in SVCI patients.

  6. Anatomical characterization of subcortical descending projections to the inferior colliculus in mouse.

    PubMed

    Patel, Mili B; Sons, Stacy; Yudintsev, Georgiy; Lesicko, Alexandria M H; Yang, Luye; Taha, Gehad A; Pierce, Scott M; Llano, Daniel A

    2017-03-01

    Descending projections from the thalamus and related structures to the midbrain are evolutionarily highly conserved. However, the basic organization of this auditory thalamotectal pathway has not yet been characterized. The purpose of this study was to obtain a better understanding of the anatomical and neurochemical features of this pathway. Analysis of the distributions of retrogradely labeled cells after focal injections of retrograde tracer into the inferior colliculus (IC) of the mouse revealed that most of the subcortical descending projections originated in the brachium of the IC and the paralaminar portions of the auditory thalamus. In addition, the vast majority of thalamotectal cells were found to be negative for the calcium-binding proteins calbindin, parvalbumin, or calretinin. Using two different strains of GAD-GFP mice, as well as immunostaining for GABA, we found that a subset of neurons in the brachium of the IC is GABAergic, suggesting that part of this descending pathway is inhibitory. Finally, dual retrograde injections into the IC and amygdala plus corpus striatum as well into the IC and auditory cortex did not reveal any double labeling. These data suggest that the thalamocollicular pathway comprises a unique population of thalamic neurons that do not contain typical calcium-binding proteins and do not project to other paralaminar thalamic forebrain targets, and that a previously undescribed descending GABAergic pathway emanates from the brachium of the IC. J. Comp. Neurol. 525:885-900, 2017. © 2016 Wiley Periodicals, Inc.

  7. Influence of Education on Subcortical Hyperintensities and Global Cognitive Status in Vascular Dementia

    PubMed Central

    Lane, Elizabeth M.; Paul, Robert H.; Moser, David J.; Fletcher, Thomas D.; Cohen, Ronald A.

    2015-01-01

    Subcortical hyperintensities (SH) on neuroimaging are a prominent feature of vascular dementia (VaD) and SH severity correlates with cognitive impairment in this population. Previous studies demonstrated that SH burden accounts for a degree of the cognitive burden among VaD patients, although it remains unclear if individual factors such as cognitive reserve influence cognitive status in VaD. To address this issue, we examined 36 individuals diagnosed with probable VaD (age = 77.56; education = 12). All individuals underwent MMSE evaluations and MRI brain scans. We predicted that individuals with higher educational attainment would exhibit less cognitive difficulty despite similar levels of SH volume, compared to individuals with less educational attainment. A regression analysis revealed that greater SH volume was associated with lower scores on the MMSE. Additionally, education moderated the relationship between SH volume and MMSE score, demonstrating that individuals with higher education had higher scores on the MMSE despite similar degrees of SH burden. These results suggest that educational attainment buffers the deleterious effects of SH burden on cognitive status among VaD patients. PMID:21385518

  8. Psychopathic traits are associated with cortical and subcortical volume alterations in healthy individuals

    PubMed Central

    Ferreira-Santos, Fernando; Almeida, Pedro R.; Barbosa, Fernando; Marques-Teixeira, João; Marsh, Abigail A.

    2015-01-01

    Research suggests psychopathy is associated with structural brain alterations that may contribute to the affective and interpersonal deficits frequently observed in individuals with high psychopathic traits. However, the regional alterations related to different components of psychopathy are still unclear. We used voxel-based morphometry to characterize the structural correlates of psychopathy in a sample of 35 healthy adults assessed with the Triarchic Psychopathy Measure. Furthermore, we examined the regional grey matter alterations associated with the components described by the triarchic model. Our results showed that, after accounting for variation in total intracranial volume, age and IQ, overall psychopathy was negatively associated with grey matter volume in the left putamen and amygdala. Additional regression analysis with anatomical regions of interests revealed total triPM score was also associated with increased lateral orbitofrontal cortex (OFC) and caudate volume. Boldness was positively associated with volume in the right insula. Meanness was positively associated with lateral OFC and striatum volume, and negatively associated with amygdala volume. Finally, disinhibition was negatively associated with amygdala volume. Results highlight the contribution of both subcortical and cortical brain alterations for subclinical psychopathy and are discussed in light of prior research and theoretical accounts about the neurobiological bases of psychopathic traits. PMID:25971600

  9. Differential susceptibility of cortical and subcortical inhibitory neurons and astrocytes in the long term following diffuse traumatic brain injury.

    PubMed

    Carron, Simone F; Yan, Edwin B; Alwis, Dasuni S; Rajan, Ramesh

    2016-12-01

    Long-term diffuse traumatic brain injury (dTBI) causes neuronal hyperexcitation in supragranular layers in sensory cortex, likely through reduced inhibition. Other forms of TBI affect inhibitory interneurons in subcortical areas but it is unknown if this occurs in cortex, or in any brain area in dTBI. We investigated dTBI effects on inhibitory neurons and astrocytes in somatosensory and motor cortex, and hippocampus, 8 weeks post-TBI. Brains were labeled with antibodies against calbindin (CB), parvalbumin (PV), calretinin (CR) and neuropeptide Y (NPY), and somatostatin (SOM) and glial fibrillary acidic protein (GFAP), a marker for astrogliosis during neurodegeneration. Despite persistent behavioral deficits in rotarod performance up to the time of brain extraction (TBI = 73.13 ± 5.23% mean ± SEM, Sham = 92.29 ± 5.56%, P < 0.01), motor cortex showed only a significant increase, in NPY neurons in supragranular layers (mean cells/mm(2) ± SEM, Sham = 16 ± 0.971, TBI = 25 ± 1.51, P = 0.001). In somatosensory cortex, only CR(+) neurons showed changes, being decreased in supragranular (TBI = 19 ± 1.18, Sham = 25 ± 1.10, P < 0.01) and increased in infragranular (TBI = 28 ± 1.35, Sham = 24 ± 1.07, P < 0.05) layers. Heterogeneous changes were seen in hippocampal staining: CB(+) decreased in dentate gyrus (TBI = 2 ± 0.382, Sham = 4 ± 0.383, P < 0.01), PV(+) increased in CA1 (TBI = 39 ± 1.26, Sham = 33 ± 1.69, P < 0.05) and CA2/3 (TBI = 26 ± 2.10, Sham = 20 ± 1.49, P < 0.05), and CR(+) decreased in CA1 (TBI = 10 ± 1.02, Sham = 14 ± 1.14, P < 0.05). Astrogliosis significantly increased in corpus callosum (TBI = 6.7 ± 0.69, Sham = 2.5 ± 0.38; P = 0.007). While dTBI effects on inhibitory neurons appear region- and type-specific, a common feature in all cases of decrease was that changes occurred in dendrite targeting interneurons involved in neuronal integration. J. Comp. Neurol. 524:3530-3560, 2016. © 2016 Wiley Periodicals, Inc.

  10. Subcortical Volumes Differ in Parkinson’s Disease Motor Subtypes: New Insights into the Pathophysiology of Disparate Symptoms

    PubMed Central

    Rosenberg-Katz, Keren; Herman, Talia; Jacob, Yael; Kliper, Efrat; Giladi, Nir; Hausdorff, Jeffery M.

    2016-01-01

    Objectives: Patients with Parkinson’s disease (PD) can be classified, based on their motor symptoms into the Postural Instability Gait Difficulty (PIGD) subtype or the Tremor Dominant (TD) subtype. Gray matter changes between the subtypes have been reported using whole brain Voxel-Based Morphometry (VBM), however, the evaluation of subcortical gray matter volumetric differences between these subtypes using automated volumetric analysis has only been studied in relatively small sample sizes and needs further study to confirm that the negative findings were not due to the sample size. Therefore, we aimed to evaluate volumetric changes in subcortical regions and their association with PD motor subtypes. Methods: Automated volumetric magnetic resonance imaging (MRI) analysis quantified the subcortical gray matter volumes of patients with PD in the PIGD subtype (n = 30), in the TD subtype (n = 30), and in 28 healthy controls (HCs). Results: Significantly lower amygdala and globus pallidus gray matter volume was detected in the PIGD, as compared to the TD subtype, with a trend for an association between globus pallidus degeneration and higher (worse) PIGD scores. Furthermore, among all the patients with PD, higher hippocampal volumes were correlated with a higher (better) dual tasking gait speed (r = 0.30, p < 0.002) and with a higher global cognitive score (r = 0.36, p < 0.0001). Lower putamen volume was correlated with a higher (worse) freezing of gait score (r = −0.28, p < 0.004), an episodic symptom which is common among the PIGD subtype. As expected, differences detected between HCs and patients in the PD subgroups included regions within the amygdala and the dorsal striatum but not the ventral striatum, a brain region that is generally considered to be more preserved in PD. Conclusions: The disparate patterns of subcortical degeneration can explain some of the differences in symptoms between the PD subtypes such as gait disturbances and cognitive functions

  11. Amyloid Precursor Protein in the Cerebral Cortex is Rapidly and Persistently Induced by Loss of Subcortical Innervation

    DTIC Science & Technology

    1993-09-01

    IS. NUMBER OF PAGES Amyloid precursor protein; nucleus basalis of Meynert; 5 Alzheimer disease , Acetylcholine 16. PRICE’CODE 17. SECURITY...observed in Alzheimer disease . Dawley rats (-225-250 g) purchased from Charles River Breeding Laboratories were subcortically lesioned at the Among...the most prominent features of Alzheimer disease following sites: (i) unilateral lesions of the nbM with (AD) are profound deficits in cortical

  12. Subcortical connections of normotopic and heterotopic neurons in sensory and motor cortices of the tish mutant rat.

    PubMed

    Schottler, F; Couture, D; Rao, A; Kahn, H; Lee, K S

    1998-05-25

    Orthograde and retrograde tracers were used to examine subcortical connections of neurons in the neurological mutant tish rat. This animal exhibits bilateral heterotopia similar to those observed in epileptic humans with subcortical band heterotopia. Terminal varicosities were labeled in the striatum, thalamus, brainstem, and spinal cord following injections of the anterograde tracer biotinylated dextran amine (BDA) into the heterotopic cortex. The general topography of corticothalamic projections was evaluated by injecting the retrograde tracer Fluoro-Gold (FG) into ventral thalamic nuclei. Retrograde labeling of small-to-medium sized neurons was observed in layer VI of topographically restricted portions of the normotopic cortex. Similar appearing cells were labeled in the neighboring portions of the underlying heterotopia; however, these neurons did not display characteristic lamination or radial orientation. Thalamocortical terminals labeled by injecting BDA into the ventroposterolateral nucleus (VPL) were observed primarily in layer IV of the medial aspect of the normotopic somatosensory cortex. In contrast, a radial column of terminals was present in the underlying heterotopia. Typical barrel labeling was found in the lateral aspect of the normotopic somatosensory cortex after injecting the ventroposteromedial nucleus (VPM), whereas more diffuse patches of labeling were observed in the underlying heterotopia. Heterotopic neurons in the tish cortex, thus, exhibit characteristic features of subcortical connectivity. Both normotopic and heterotopic neurons in the tish brain project to appropriate subcortical sites and establish bidirectional topographic connections with the thalamus. These results suggest that primary sensory-motor information is represented in a parallel manner in the normotopic and heterotopic cortices of the tish rat.

  13. NeuN+ neuronal nuclei in non-human primate prefrontal cortex and subcortical white matter after clozapine exposure.

    PubMed

    Halene, Tobias B; Kozlenkov, Alexey; Jiang, Yan; Mitchell, Amanda C; Javidfar, Behnam; Dincer, Aslihan; Park, Royce; Wiseman, Jennifer; Croxson, Paula L; Giannaris, Eustathia Lela; Hof, Patrick R; Roussos, Panos; Dracheva, Stella; Hemby, Scott E; Akbarian, Schahram

    2016-02-01

    Increased neuronal densities in subcortical white matter have been reported for some cases with schizophrenia. The underlying cellular and molecular mechanisms remain unresolved. We exposed 26 young adult macaque monkeys for 6 months to either clozapine, haloperidol or placebo and measured by structural MRI frontal gray and white matter volumes before and after treatment, followed by observer-independent, flow-cytometry-based quantification of neuronal and non-neuronal nuclei and molecular fingerprinting of cell-type specific transcripts. After clozapine exposure, the proportion of nuclei expressing the neuronal marker NeuN increased by approximately 50% in subcortical white matter, in conjunction with a more subtle and non-significant increase in overlying gray matter. Numbers and proportions of nuclei expressing the oligodendrocyte lineage marker, OLIG2, and cell-type specific RNA expression patterns, were maintained after antipsychotic drug exposure. Frontal lobe gray and white matter volumes remained indistinguishable between antipsychotic-drug-exposed and control groups. Chronic clozapine exposure increases the proportion of NeuN+ nuclei in frontal subcortical white matter, without alterations in frontal lobe volumes or cell type-specific gene expression. Further exploration of neurochemical plasticity in non-human primate brain exposed to antipsychotic drugs is warranted.

  14. Cortical–Subcortical Interactions in Hypersomnia Disorders: Mechanisms Underlying Cognitive and Behavioral Aspects of the Sleep–Wake Cycle

    PubMed Central

    Larson-Prior, Linda J.; Ju, Yo-El; Galvin, James E.

    2014-01-01

    Subcortical circuits mediating sleep–wake functions have been well characterized in animal models, and corroborated by more recent human studies. Disruptions in these circuits have been identified in hypersomnia disorders (HDs) such as narcolepsy and Kleine–Levin Syndrome, as well as in neurodegenerative disorders expressing excessive daytime sleepiness. However, the behavioral expression of sleep–wake functions is not a simple on-or-off state determined by subcortical circuits, but encompasses a complex range of behaviors determined by the interaction between cortical networks and subcortical circuits. While conceived as disorders of sleep, HDs are equally disorders of wake, representing a fundamental instability in neural state characterized by lapses of alertness during wake. These episodic lapses in alertness and wakefulness are also frequently seen in neurodegenerative disorders where electroencephalogram demonstrates abnormal function in cortical regions associated with cognitive fluctuations (CFs). Moreover, functional connectivity MRI shows instability of cortical networks in individuals with CFs. We propose that the inability to stabilize neural state due to disruptions in the sleep–wake control networks is common to the sleep and cognitive dysfunctions seen in hypersomnia and neurodegenerative disorders. PMID:25309500

  15. Contralesional Cortical Structural Reorganization Contributes to Motor Recovery after Sub-Cortical Stroke: A Longitudinal Voxel-Based Morphometry Study

    PubMed Central

    Cai, Jianxin; Ji, Qiling; Xin, Ruiqiang; Zhang, Dianping; Na, Xu; Peng, Ruchen; Li, Kuncheng

    2016-01-01

    Although changes in brain gray matter after stroke have been identified in some neuroimaging studies, lesion heterogeneity and individual variability make the detection of potential neuronal reorganization difficult. This study attempted to investigate the potential structural cortical reorganization after sub-cortical stroke using a longitudinal voxel-based gray matter volume (GMV) analysis. Eleven right-handed patients with first-onset, subcortical, ischemic infarctions involving the basal ganglia regions underwent structural magnetic resonance imaging in addition to National Institutes of Health Stroke Scale (NIHSS) and Motricity Index (MI) assessments in the acute (<5 days) and chronic stages (1 year later). The GMVs were calculated and compared between the two stages using nonparametric permutation paired t-tests. Moreover, the Spearman correlations between the GMV changes and clinical recoveries were analyzed. Compared with the acute stage, significant decreases in GMV were observed in the ipsilesional (IL) precentral gyrus (PreCG), paracentral gyrus (ParaCG), and contralesional (CL) cerebellar lobule VII in the chronic stage. Additionally, significant increases in GMV were found in the CL orbitofrontal cortex (OFC) and middle (MFG) and inferior frontal gyri (IFG). Furthermore, severe GMV atrophy in the IL PreCG predicted poorer clinical recovery, and greater GMV increases in the CL OFG and MFG predicted better clinical recovery. Our findings suggest that structural reorganization of the CL “cognitive” cortices might contribute to motor recovery after sub-cortical stroke. PMID:27536229

  16. Dopamine Modulation of Emotional Processing in Cortical and Subcortical Neural Circuits: Evidence for a Final Common Pathway in Schizophrenia?

    PubMed Central

    2007-01-01

    The neural regulation of emotional perception, learning, and memory is essential for normal behavioral and cognitive functioning. Many of the symptoms displayed by individuals with schizophrenia may arise from fundamental disturbances in the ability to accurately process emotionally salient sensory information. The neurotransmitter dopamine (DA) and its ability to modulate neural regions involved in emotional learning, perception, and memory formation has received considerable research attention as a potential final common pathway to account for the aberrant emotional regulation and psychosis present in the schizophrenic syndrome. Evidence from both human neuroimaging studies and animal-based research using neurodevelopmental, behavioral, and electrophysiological techniques have implicated the mesocorticolimbic DA circuit as a crucial system for the encoding and expression of emotionally salient learning and memory formation. While many theories have examined the cortical-subcortical interactions between prefrontal cortical regions and subcortical DA substrates, many questions remain as to how DA may control emotional perception and learning and how disturbances linked to DA abnormalities may underlie the disturbed emotional processing in schizophrenia. Beyond the mesolimbic DA system, increasing evidence points to the amygdala-prefrontal cortical circuit as an important processor of emotionally salient information and how neurodevelopmental perturbances within this circuitry may lead to dysregulation of DAergic modulation of emotional processing and learning along this cortical-subcortical emotional processing circuit. PMID:17519393

  17. TLR9 re-expression in cancer cells extends the S-phase and stabilizes p16INK4a protein expression

    PubMed Central

    Parroche, P; Roblot, G; Le Calvez-Kelm, F; Tout, I; Marotel, M; Malfroy, M; Durand, G; McKay, J; Ainouze, M; Carreira, C; Allatif, O; Traverse-Glehen, A; Mendiola, M; Pozo-Kreilinger, J J; Caux, C; Tommasino, M; Goutagny, N; Hasan, U A

    2016-01-01

    Toll-like receptor 9 (TLR9) recognizes bacterial, viral or cell damage-associated DNA, which initiates innate immune responses. We have previously shown that TLR9 expression is downregulated in several viral induced cancers including HPV16-induced cervical neoplasia. Findings supported that downregulation of TLR9 expression is involved in loss of anti-viral innate immunity allowing an efficient viral replication. Here we investigated the role of TLR9 in altering the growth of transformed epithelial cells. Re-introducing TLR9 under the control of an exogenous promoter in cervical or head and neck cancer patient-derived cells reduced cell proliferation, colony formation and prevented independent growth of cells under soft agar. Neither TLR3, 7, nor the TLR adapter protein MyD88 expression had any effect on cell proliferation, indicating that TLR9 has a unique role in controlling cell growth. The reduction of cell growth was not due to apoptosis or necrosis, yet we observed that cells expressing TLR9 were slower in entering the S-phase of the cell cycle. Microarray-based gene expression profiling analysis highlighted a strong interferon (IFN) signature in TLR9-expressing head and neck cancer cells, with an increase in IFN-type I and IL-29 expression (IFN-type III), yet neither IFN-type I nor IL-29 production was responsible for the block in cell growth. We observed that the protein half-life of p16INK4a was increased in TLR9-expressing cells. Taken together, these data show for the first time that TLR9 affects the cell cycle by regulating p16INK4a post-translational modifications and highlights the role of TLR9 in the events that lead to carcinogenesis. PMID:27454079

  18. Startle reduces recall of a recently learned internal model.

    PubMed

    Wright, Zachary; Patton, James L; Ravichandran, Venn

    2011-01-01

    Recent work has shown that preplanned motor programs are released early from subcortical areas by the using a startling acoustic stimulus (SAS). Our question is whether this response might also contain a recently learned internal model, which draws on experience to predict and compensate for expected perturbations in a feedforward manner. Studies of adaptation to robotic forces have shown some evidence of this, but were potentially confounded by cocontraction caused by startle. We performed a new adaptation experiment using a visually distorted field that could not be confounded by cocontraction. We found that in all subjects that exhibited startle, the startle stimulus (1) reduced performance of the recently learned task (2) reduced after-effect magnitudes. Because startle reduced but did not eliminate the recall of learned control, we suggest that multiple neural centers (cortical and subcortical) are involved in such learning and adaptation, which can impact training areas such as piloting, teleoperation, sports, and rehabilitation.

  19. The re-expression of the epigenetically silenced e-cadherin gene by a polyamine analogue lysine-specific demethylase-1 (LSD1) inhibitor in human acute myeloid leukemia cell lines.

    PubMed

    Murray-Stewart, Tracy; Woster, Patrick M; Casero, Robert A

    2014-03-01

    Aberrant epigenetic silencing of tumor suppressor genes is a common feature observed during the transformation process of many cancers, including those of hematologic origin. Histone modifications, including acetylation, phosphorylation, and methylation, collaborate with DNA CpG island methylation to regulate gene expression. The dynamic process of histone methylation is the latest of these epigenetic modifications to be described, and the identification and characterization of LSD1 as a demethylase of lysine 4 of histone H3 (H3K4) has confirmed that both the enzyme and the modified histone play important roles as regulators of gene expression. LSD1 activity contributes to the suppression of gene expression by demethylating promoter-region mono- and dimethyl-H3K4 histone marks that are associated with active gene expression. As most post-translational modifications are reversible, the enzymes involved in the modification of histones have become targets for chemotherapeutic intervention. In this study, we examined the effects of the polyamine analogue LSD1 inhibitor 2d (1,15-bis{N (5)-[3,3-(diphenyl)propyl]-N(1)-biguanido}-4,12-diazapentadecane) in human acute myeloid leukemia (AML) cell lines. In each line studied, 2d evoked cytotoxicity and inhibited LSD1 activity, as evidenced by increases in the global levels of mono- and di-methylated H3K4 proteins. Global increases in other chromatin modifications were also observed following exposure to 2d, suggesting a broad response to this compound with respect to chromatin regulation. On a gene-specific level, treatment with 2d resulted in the re-expression of e-cadherin, a tumor suppressor gene frequently silenced by epigenetic modification in AML. Quantitative chromatin immunoprecipitation analysis of the e-cadherin promoter further confirmed that this re-expression was concurrent with changes in both active and repressive histone marks that were consistent with LSD1 inhibition. As hematologic malignancies have

  20. Developmentally Sensitive Interaction Effects of Genes and the Social Environment on Total and Subcortical Brain Volumes

    PubMed Central

    Arias Vásquez, Alejandro; Franke, Barbara; Hoekstra, Pieter J.; Heslenfeld, Dirk J.; Oosterlaan, Jaap; Faraone, Stephen V.

    2016-01-01

    Smaller total brain and subcortical volumes have been linked to psychopathology including attention-deficit/hyperactivity disorder (ADHD). Identifying mechanisms underlying these alterations, therefore, is of great importance. We investigated the role of gene-environment interactions (GxE) in interindividual variability of total gray matter (GM), caudate, and putamen volumes. Brain volumes were derived from structural magnetic resonance imaging scans in participants with (N = 312) and without ADHD (N = 437) from N = 402 families (age M = 17.00, SD = 3.60). GxE effects between DAT1, 5-HTT, and DRD4 and social environments (maternal expressed warmth and criticism; positive and deviant peer affiliation) as well as the possible moderating effect of age were examined using linear mixed modeling. We also tested whether findings depended on ADHD severity. Deviant peer affiliation was associated with lower caudate volume. Participants with low deviant peer affiliations had larger total GM volumes with increasing age. Likewise, developmentally sensitive GxE effects were found on total GM and putamen volume. For total GM, differential age effects were found for DAT1 9-repeat and HTTLPR L/L genotypes, depending on the amount of positive peer affiliation. For putamen volume, DRD4 7-repeat carriers and DAT1 10/10 homozygotes showed opposite age relations depending on positive peer affiliation and maternal criticism, respectively. All results were independent of ADHD severity. The presence of differential age-dependent GxE effects might explain the diverse and sometimes opposing results of environmental and genetic effects on brain volumes observed so far. PMID:27218681

  1. Blood Pressure After Recent Stroke: Baseline Findings From the Secondary Prevention of Small Subcortical Strokes Trial

    PubMed Central

    White, Carole L.; Pergola, Pablo E.; Szychowski, Jeff M.; Talbert, Robert; Benavente, Oscar R.

    2013-01-01

    BACKGROUND Hypertension is the most powerful risk factor for stroke. The aim of this study was to characterize baseline blood pressure in participants in the Secondary Prevention of Small Subcortical Strokes trial. METHODS For this cross-sectional analysis, participants were categorized by baseline systolic blood pressure (SBP) < 120, 120–139, 140–159, 160–179, and ≥ 180mm Hg and compared on demographic and clinical characteristics. Predictors of SBP < 140mm Hg were examined. RESULTS Mean SBP was 143±19mm Hg while receiving an average of 1.7 antihypertensive medications; SBP ≥ 140mm Hg for 53% and ≥ 160 mm Hg for 18% of the 3,020 participants. Higher SBP was associated with a history of hypertension and hypertension for longer duration (both P < 0.0001). Higher SBPs were associated with more extensive white matter disease on magnetic resonance imaging (P < 0.0001). There were significant differences in entry-level SBP when participants were categorized by race and region (both P < 0.0001). Black participants were more likely to have SBP ≥ 140mm Hg. Multivariable logistic regression showed an independent effect for region with those from Canada more likely (odds ratio = 1.7; 95% confidence interval, 1.29, 2.32) to have SBP < 140mm Hg compared with participants from United States. CONCLUSIONS In this cohort with symptomatic lacunar stroke, more than half had uncontrolled hypertension at approximately 2.5 months after stroke. Regional, racial, and clinical differences should be considered to improve control and prevent recurrent stroke. CLINICAL TRIALS REGISTRATION Trial Number NCT00059306 PMID:23736109

  2. The prefrontal cortex achieves inhibitory control by facilitating subcortical motor pathway connectivity.

    PubMed

    Rae, Charlotte L; Hughes, Laura E; Anderson, Michael C; Rowe, James B

    2015-01-14

    Communication between the prefrontal cortex and subcortical nuclei underpins the control and inhibition of behavior. However, the interactions in such pathways remain controversial. Using a stop-signal response inhibition task and functional imaging with analysis of effective connectivity, we show that the lateral prefrontal cortex influences the strength of communication between regions in the frontostriatal motor system. We compared 20 generative models that represented alternative interactions between the inferior frontal gyrus, presupplementary motor area (preSMA), subthalamic nucleus (STN), and primary motor cortex during response inhibition. Bayesian model selection revealed that during successful response inhibition, the inferior frontal gyrus modulates an excitatory influence of the preSMA on the STN, thereby amplifying the downstream polysynaptic inhibition from the STN to the motor cortex. Critically, the strength of the interaction between preSMA and STN, and the degree of modulation by the inferior frontal gyrus, predicted individual differences in participants' stopping performance (stop-signal reaction time). We then used diffusion-weighted imaging with tractography to assess white matter structure in the pathways connecting these three regions. The mean diffusivity in tracts between preSMA and the STN, and between the inferior frontal gyrus and STN, also predicted individual differences in stopping efficiency. Finally, we found that white matter structure in the tract between preSMA and STN correlated with effective connectivity of the same pathway, providing important cross-modal validation of the effective connectivity measures. Together, the results demonstrate the network dynamics and modulatory role of the prefrontal cortex that underpin individual differences in inhibitory control.

  3. Functional grouping and cortical–subcortical interactions in emotion: A meta-analysis of neuroimaging studies

    PubMed Central

    Kober, Hedy; Barrett, Lisa Feldman; Joseph, Josh; Bliss-Moreau, Eliza; Lindquist, Kristen; Wager, Tor D.

    2009-01-01

    We performed an updated quantitative meta-analysis of 162 neuroimaging studies of emotion using a novel multi-level kernel-based approach, focusing on locating brain regions consistently activated in emotional tasks and their functional organization into distributed functional groups, independent of semantically defined emotion category labels (e.g., “anger,” “fear”). Such brain-based analyses are critical if our ways of labeling emotions are to be evaluated and revised based on consistency with brain data. Consistent activations were limited to specific cortical sub-regions, including multiple functional areas within medial, orbital, and inferior lateral frontal cortices. Consistent with a wealth of animal literature, multiple subcortical activations were identified, including amygdala, ventral striatum, thalamus, hypothalamus, and periaqueductal gray. We used multivariate parcellation and clustering techniques to identify groups of co-activated brain regions across studies. These analyses identified six distributed functional groups, including medial and lateral frontal groups, two posterior cortical groups, and paralimbic and core limbic/brainstem groups. These functional groups provide information on potential organization of brain regions into large-scale networks. Specific follow-up analyses focused on amygdala, periaqueductal gray (PAG), and hypothalamic (Hy) activations, and identified frontal cortical areas co-activated with these core limbic structures. While multiple areas of frontal cortex co-activated with amygdala sub-regions, a specific region of dorsomedial prefrontal cortex (dmPFC, Brodmann’s Area 9/32) was the only area co-activated with both PAG and Hy. Subsequent mediation analyses were consistent with a pathway from dmPFC through PAG to Hy. These results suggest that medial frontal areas are more closely associated with core limbic activation than their lateral counterparts, and that dmPFC may play a particularly important role in the

  4. Subcortical Modulation of Attentional Control by Second-Generation Antipsychotics in First-Episode Psychosis

    PubMed Central

    Ikuta, Toshikazu; Robinson, Delbert G.; Gallego, Juan A.; Peters, Bart D.; Gruner, Patricia; Kane, John; John, Majnu; Sevy, Serge; Malhotra, Anil K.; Szeszko, Philip R.

    2013-01-01

    Psychotic disorders are characterized by significant deficits in attentional control, but the neurobiological mechanisms underlying these deficits early in the course of illness prior to extensive pharmacotherapy are not well understood. Moreover, little is known regarding the symptom and brain changes associated with amelioration of attentional impairments through antipsychotic pharmacotherapy. In this study 14 male patients experiencing a first-episode of psychosis with minimal prior antipsychotic treatment completed an attentional control task while undergoing functional magnetic resonance imaging at the onset of treatment with a second generation antipsychotic (risperidone or aripiprazole) in a double blind randomized clinical trial and then again following approximately 12 weeks of treatment. In addition, fourteen age-, and performance-matched healthy male volunteers who were not treated completed the same task at a baseline timepoint and then again following 12 weeks. Patients showed significantly greater activation than healthy volunteers in the right globus pallidus, left thalamus, and right thalamus at the time of the baseline scan. Among patients there was a significant reduction in right globus pallidus blood-oxygen level dependent (BOLD) response following antipsychotic treatment that correlated significantly with improvement in response accuracy and reductions in thought disturbance. No changes in globus pallidus activation were observed in healthy volunteers over this time period. These preliminary findings suggest that improvement in attentional control and concomitant reductions in thought disturbance in first-episode psychosis may be associated with reductions in subcortical activity following administration of second-generation antipsychotics early in the course of illness. These findings have implications for understanding how changes in basal ganglia activity may be linked to improvements in attentional control through antipsychotics. PMID

  5. Subcortical modulation of attentional control by second-generation antipsychotics in first-episode psychosis.

    PubMed

    Ikuta, Toshikazu; Robinson, Delbert G; Gallego, Juan A; Peters, Bart D; Gruner, Patricia; Kane, John; John, Majnu; Sevy, Serge; Malhotra, Anil K; Szeszko, Philip R

    2014-02-28

    Psychotic disorders are characterized by significant deficits in attentional control, but the neurobiological mechanisms underlying these deficits early in the course of illness prior to extensive pharmacotherapy are not well understood. Moreover, little is known regarding the symptom and brain changes associated with amelioration of attentional impairments through antipsychotic pharmacotherapy. In this study 14 male patients experiencing a first-episode of psychosis with minimal prior antipsychotic treatment completed an attentional control task while undergoing functional magnetic resonance imaging at the onset of treatment with a second generation antipsychotic (risperidone or aripiprazole) in a double blind randomized clinical trial and then again following approximately 12 weeks of treatment. In addition, 14 age-, and performance-matched healthy male volunteers who were not treated completed the same task at a baseline timepoint and then again following 12 weeks. Patients showed significantly greater activation than healthy volunteers in the right globus pallidus, left thalamus, and right thalamus at the time of the baseline scan. Among patients there was a significant reduction in right globus pallidus blood-oxygen level dependent (BOLD) response following antipsychotic treatment that correlated significantly with improvement in response accuracy and reductions in thought disturbance. No changes in globus pallidus activation were observed in healthy volunteers over this time period. These preliminary findings suggest that improvement in attentional control and concomitant reductions in thought disturbance in first-episode psychosis may be associated with reductions in subcortical activity following administration of second-generation antipsychotics early in the course of illness. These findings have implications for understanding how changes in basal ganglia activity may be linked to improvements in attentional control through antipsychotics.

  6. Frequency-dependent effects of background noise on subcortical response timing.

    PubMed

    Tierney, A; Parbery-Clark, A; Skoe, E; Kraus, N

    2011-12-01

    The addition of background noise to an auditory signal delays brainstem response timing. This effect has been extensively documented using manual peak selection. Peak picking, however, is impractical for large-scale studies of spectrotemporally complex stimuli, and leaves open the question of whether noise-induced delays are frequency-dependent or occur across the frequency spectrum. Here we use an automated, objective method to examine phase shifts between auditory brainstem responses to a speech sound (/da/) presented with and without background noise. We predicted that shifts in neural response timing would also be reflected in frequency-specific phase shifts. Our results indicate that the addition of background noise causes phase shifts across the subcortical response spectrum (70-1000 Hz). However, this noise-induced delay is not uniform such that some frequency bands show greater shifts than others: low-frequency phase shifts (300-500 Hz) are largest during the response to the consonant-vowel formant transition (/d/), while high-frequency shifts (720-1000 Hz) predominate during the response to the steady-state vowel (/a/). Most importantly, phase shifts occurring in specific frequency bands correlate strongly with shifts in the latencies of the predominant peaks in the auditory brainstem response, while phase shifts in other frequency bands do not. This finding confirms the validity of phase shift detection as an objective measure of timing differences and reveals that this method detects noise-induced shifts in timing that may not be captured by traditional peak latency measurements.

  7. Subcortical gray matter changes in transgender subjects after long-term cross-sex hormone administration.

    PubMed

    Seiger, Rene; Hahn, Andreas; Hummer, Allan; Kranz, Georg S; Ganger, Sebastian; Woletz, Michael; Kraus, Christoph; Sladky, Ronald; Kautzky, Alexander; Kasper, Siegfried; Windischberger, Christian; Lanzenberger, Rupert

    2016-12-01

    Sex-steroid hormones are primarily involved in sexual differentiation and development and are thought to underlie processes related to cognition and emotion. However, divergent results have been reported concerning the effects of hormone administration on brain structure including side effects like brain atrophy and dementia. Cross-sex hormone therapy in transgender subjects offers a unique model for studying the effects of sex hormones on the living human brain. In this study, 25 Female-to-Male (FtM) and 14 Male-to-Female (MtF) subjects underwent MRI examinations at baseline and after a period of at least 4-months of continuous cross-sex hormone administration. While MtFs received estradiol and anti-androgens, FtM subjects underwent high-dose testosterone treatment. The longitudinal processing stream of the FreeSurfer software suite was used for the automated assessment and delineation of brain volumes to assess the structural changes over the treatment period of cross-sex hormone administration. Most prominent results were found for MtFs receiving estradiol and anti-androgens in the form of significant decreases in the hippocampal region. Further analysis revealed that these decreases were reflected by increases in the ventricles. Additionally, changes in progesterone levels correlated with changes in gray matter structures in MtF subjects. In line with prior studies, our results indicate hormonal influences on subcortical structures related to memory and emotional processing. Additionally, this study adds valuable knowledge that progesterone may play an important role in this process.

  8. Volume changes and brain-behavior relationships in white matter and subcortical gray matter in children with prenatal alcohol exposure.

    PubMed

    Gautam, Prapti; Lebel, Catherine; Narr, Katherine L; Mattson, Sarah N; May, Philip A; Adnams, Colleen M; Riley, Edward P; Jones, Kenneth L; Kan, Eric C; Sowell, Elizabeth R

    2015-06-01

    Children with prenatal alcohol exposure (PAE) may have cognitive, behavioral and brain abnormalities. Here, we compare rates of white matter and subcortical gray matter volume change in PAE and control children, and examine relationships between annual volume change and arithmetic ability, behavior, and executive function. Participants (n = 75 PAE/64 control; age: 7.1-15.9 years) each received two structural magnetic resonance scans, ~2 years apart. Assessments included Wechsler Intelligence Scale for Children (WISC-IV), the Child Behavior Checklist and the Behavior Rating Inventory of Executive Function. Subcortical white and gray volumes were extracted for each hemisphere. Group volume differences were tested using false discovery rate (q < 0.05). Analyses examined group-by-age interactions and group-score interactions for correlations between change in volume and raw behavioral scores. Results showed that subjects with PAE had smaller volumes than control subjects across the brain. Significant group-score interactions were found in temporal and parietal regions for WISC arithmetic scores and in frontal and parietal regions for behavioral measures. Poorer cognitive/ behavioral outcomes were associated with larger volume increases in PAE, while control subjects generally showed no significant correlations. In contrast with previous results demonstrating different trajectories of cortical volume change in PAE, our results show similar rates of subcortical volume growth in subjects with PAE and control subjects. We also demonstrate abnormal brain-behavior relationships in subjects with PAE, suggesting different use of brain resources. Our results are encouraging in that, due to the stable volume differences, there may be an extended window of opportunity for intervention in children with PAE.

  9. Random motor generation in a finger tapping task: influence of spatial contingency and of cortical and subcortical hemispheric brain lesions

    PubMed Central

    Annoni, J.; Pegna, A.

    1997-01-01

    OBJECTIVE—To test the hypothesis that, during random motor generation, the spatial contingencies inherent to the task would induce additional preferences in normal subjects, shifting their performances farther from randomness. By contrast, perceptual or executive dysfunction could alter these task related biases in patients with brain damage.
METHODS—Two groups of patients, with right and left focal brain lesions, as well as 25 right handed subjects matched for age and handedness were asked to execute a random choice motor task—namely, to generate a random series of 180 button presses from a set of 10 keys placed vertically in front of them.
RESULTS—In the control group, as in the left brain lesion group, motor generation was subject to deviations from theoretical expected randomness, similar to those when numbers are generated mentally, as immediate repetitions (successive presses on the same key) are avoided. However, the distribution of button presses was also contingent on the topographic disposition of the keys: the central keys were chosen more often than those placed at extreme positions. Small distances were favoured, particularly with the left hand. These patterns were influenced by implicit strategies and task related contingencies.
 By contrast, right brain lesion patients with frontal involvement tended to show a more square distribution of key presses—that is, the number of key presses tended to be more equally distributed. The strategies were also altered by brain lesions: the number of immediate repetitions was more frequent when the lesion involved the right frontal areas yielding a random generation nearer to expected theoretical randomness. The frequency of adjacent key presses was increased by right anterior and left posterior cortical as well as by right subcortical lesions, but decreased by left subcortical lesions.
CONCLUSIONS—Depending on the side of the lesion and the degree of cortical-subcortical involvement, the

  10. Paranormal and religious beliefs may be mediated differentially by subcortical and cortical phenomenological processes of the temporal (limbic) lobes.

    PubMed

    Persinger, M A

    1993-02-01

    The vectorial hemisphericity concept predicts that endorsements of beliefs in paranormal phenomena are associated with elevated subcortical (complex partial epileptic-like signs) temporal lobe experiences while endorsements of religious beliefs are associated with experiences of the right (cortical) hemispheric equivalent (the sensed presence) of the linguistic sense of self. Partial correlation analyses, which removed the expected shared variance, supported this hypothesis for 400 men and 400 women; religious affiliation did not contribute any statistically significant influence. However, agreements with extreme religious beliefs, such as killing others in God's name, were associated with weekly church attendance and were primarily endorsed by men but not by women.

  11. Observations on regional cerebral blood flow in cortical and subcortical structures during language production in normal man

    SciTech Connect

    Wallesch, C.W.; Henriksen, L.; Kornhuber, H.H.; Paulson, O.B.

    1985-07-01

    Regional cerebral blood flow (rCBF) was studied by single photon emission computerized tomography (SPECT) of inhaled xenon-133 in six normal volunteers during various language, articulatory, and control conditions. Language production increased rCBF in predominantly left-sided cortical and subcortical areas. The involved regions were anatomically related to a left frontal area (Broca's), to both caudate nuclei, to a left thalamic/pallidal area, and bilaterally in retrorolandic areas. The failure to demonstrate lateralized retrorolandic activity is thought to reflect the complexity of the tasks.

  12. An improved FSL-FIRST pipeline for subcortical gray matter segmentation to study abnormal brain anatomy using quantitative susceptibility mapping (QSM).

    PubMed

    Feng, Xiang; Deistung, Andreas; Dwyer, Michael G; Hagemeier, Jesper; Polak, Paul; Lebenberg, Jessica; Frouin, Frédérique; Zivadinov, Robert; Reichenbach, Jürgen R; Schweser, Ferdinand

    2017-02-07

    Accurate and robust segmentation of subcortical gray matter (SGM) nuclei is required in many neuroimaging applications. FMRIB's Integrated Registration and Segmentation Tool (FIRST) is one of the most popular software tools for automated subcortical segmentation based on T1-weighted (T1w) images. In this work, we demonstrate that FIRST tends to produce inaccurate SGM segmentation results in the case of abnormal brain anatomy, such as present in atrophied brains, due to a poor spatial match of the subcortical structures with the training data in the MNI space as well as due to insufficient contrast of SGM structures on T1w images. Consequently, such deviations from the average brain anatomy may introduce analysis bias in clinical studies, which may not always be obvious and potentially remain unidentified. To improve the segmentation of subcortical nuclei, we propose to use FIRST in combination with a special Hybrid image Contrast (HC) and Non-Linear (nl) registration module (HC-nlFIRST), where the hybrid image contrast is derived from T1w images and magnetic susceptibility maps to create subcortical contrast that is similar to that in the Montreal Neurological Institute (MNI) template. In our approach, a nonlinear registration replaces FIRST's default linear registration, yielding a more accurate alignment of the input data to the MNI template. We evaluated our method on 82 subjects with particularly abnormal brain anatomy, selected from a database of >2000 clinical cases. Qualitative and quantitative analyses revealed that HC-nlFIRST provides improved segmentation compared to the default FIRST method.

  13. Subcortical brain volume abnormalities in 2028 individuals with schizophrenia and 2540 healthy controls via the ENIGMA consortium

    PubMed Central

    van Erp, T G M; Hibar, D P; Rasmussen, J M; Glahn, D C; Pearlson, G D; Andreassen, O A; Agartz, I; Westlye, L T; Haukvik, U K; Dale, A M; Melle, I; Hartberg, C B; Gruber, O; Kraemer, B; Zilles, D; Donohoe, G; Kelly, S; McDonald, C; Morris, D W; Cannon, D M; Corvin, A; Machielsen, M W J; Koenders, L; de Haan, L; Veltman, D J; Satterthwaite, T D; Wolf, D H; Gur, R C; Gur, R E; Potkin, S G; Mathalon, D H; Mueller, B A; Preda, A; Macciardi, F; Ehrlich, S; Walton, E; Hass, J; Calhoun, V D; Bockholt, H J; Sponheim, S R; Shoemaker, J M; van Haren, N E M; Pol, H E H; Ophoff, R A; Kahn, R S; Roiz-Santiañez, R; Crespo-Facorro, B; Wang, L; Alpert, K I; Jönsson, E G; Dimitrova, R; Bois, C; Whalley, H C; McIntosh, A M; Lawrie, S M; Hashimoto, R; Thompson, P M; Turner, J A

    2016-01-01

    The profile of brain structural abnormalities in schizophrenia is still not fully understood, despite decades of research using brain scans. To validate a prospective meta-analysis approach to analyzing multicenter neuroimaging data, we analyzed brain MRI scans from 2028 schizophrenia patients and 2540 healthy controls, assessed with standardized methods at 15 centers worldwide. We identified subcortical brain volumes that differentiated patients from controls, and ranked them according to their effect sizes. Compared with healthy controls, patients with schizophrenia had smaller hippocampus (Cohen's d=−0.46), amygdala (d=−0.31), thalamus (d=−0.31), accumbens (d=−0.25) and intracranial volumes (d=−0.12), as well as larger pallidum (d=0.21) and lateral ventricle volumes (d=0.37). Putamen and pallidum volume augmentations were positively associated with duration of illness and hippocampal deficits scaled with the proportion of unmedicated patients. Worldwide cooperative analyses of brain imaging data support a profile of subcortical abnormalities in schizophrenia, which is consistent with that based on traditional meta-analytic approaches. This first ENIGMA Schizophrenia Working Group study validates that collaborative data analyses can readily be used across brain phenotypes and disorders and encourages analysis and data sharing efforts to further our understanding of severe mental illness. PMID:26033243

  14. Effects of cerebrovascular disease and amyloid beta burden on cognition in subjects with subcortical vascular cognitive impairment.

    PubMed

    Park, Jae-Hyun; Seo, Sang Won; Kim, Changsoo; Kim, Sook Hui; Kim, Geon Ha; Kim, Sung Tae; Jeon, Seun; Lee, Jong Min; Oh, Seung Jun; Kim, Jae Seung; Choe, Yearn Seong; Lee, Kyung-Han; Shin, Ji Soo; Kim, Chi Hun; Noh, Young; Cho, Hanna; Yoon, Cindy W; Kim, Hee Jin; Ye, Byoung Seok; Ewers, Michael; Weiner, Michael W; Lee, Jae-Hong; Werring, David J; Na, Duk L

    2014-01-01

    Cerebrovascular disease (CVD) and amyloid burden are the most frequent pathologies in subjects with cognitive impairment. However, the relationship between CVD, amyloid burden, and cognition are largely unknown. We aimed to evaluate whether CVD (lacunes, white matter hyperintensities, and microbleeds) and amyloid burden (Pittsburgh compound B [PiB] retention ratio) contribute to cognitive impairment independently or interactively. We recruited 136 patients with subcortical vascular cognitive impairment who underwent magnetic resonance imaging, PiB-positron emission tomography, and neuropsychological testing. The number of lacunes was associated with memory, frontal dysfunctions, and disease severity. The volume of white matter hyperintensities and the PiB retention ratio were associated only with memory dysfunction. There was no direct correlation between CVD markers and PiB retention ratio except that the number of lacunes was negatively correlated with the PiB retention ratio. In addition, there were no interactive effects of CVD and PiB retention ratio on cognition. Our findings suggest that CVD and amyloid burden contribute independently and not interactively to specific patterns of cognitive dysfunction in patients with subcortical vascular cognitive impairment.

  15. Emotional perception: Correspondence of early and late event-related potentials with cortical and subcortical functional MRI

    PubMed Central

    Sabatinelli, Dean; Keil, Andreas; Frank, David W.; Lang, Peter J.

    2012-01-01

    Using a picture perception task, here we investigate the relationship of early occipitotemporal and later centroparietal emotion-modulated event-related potentials (ERPs) in one sample to functional magnetic resonance imaging (fMRI) estimates of neural activity in another sample in a replicated experiment. Using this approach, we aimed to link effects found in time-resolved electrocortical measures to specific cerebral structures across individual emotional and nonemotional picture stimuli. The centroparietal late positive potential (LPP) showed covariation with emotion-modulated regions of hemodynamic activation across multiple dorsal and ventral visual cortical structures, while the early occipitotemporal potential was not reliably associated. Subcortical and corticolimbic structures involved in the perception of motivationally relevant stimuli also related to modulation of the LPP, and were modestly associated to the amplitude of the early occipitotemporal potential. These data suggest that early occipitotemporal potentials may reflect multiple sources of modulation including motivational relevance, and supports the perspective that the slow-wave LPP represents aggregate cortical and subcortical structures involved in emotional discrimination. PMID:22560889

  16. Subcortical brain volume abnormalities in 2028 individuals with schizophrenia and 2540 healthy controls via the ENIGMA consortium.

    PubMed

    van Erp, T G M; Hibar, D P; Rasmussen, J M; Glahn, D C; Pearlson, G D; Andreassen, O A; Agartz, I; Westlye, L T; Haukvik, U K; Dale, A M; Melle, I; Hartberg, C B; Gruber, O; Kraemer, B; Zilles, D; Donohoe, G; Kelly, S; McDonald, C; Morris, D W; Cannon, D M; Corvin, A; Machielsen, M W J; Koenders, L; de Haan, L; Veltman, D J; Satterthwaite, T D; Wolf, D H; Gur, R C; Gur, R E; Potkin, S G; Mathalon, D H; Mueller, B A; Preda, A; Macciardi, F; Ehrlich, S; Walton, E; Hass, J; Calhoun, V D; Bockholt, H J; Sponheim, S R; Shoemaker, J M; van Haren, N E M; Hulshoff Pol, H E; Pol, H E H; Ophoff, R A; Kahn, R S; Roiz-Santiañez, R; Crespo-Facorro, B; Wang, L; Alpert, K I; Jönsson, E G; Dimitrova, R; Bois, C; Whalley, H C; McIntosh, A M; Lawrie, S M; Hashimoto, R; Thompson, P M; Turner, J A

    2016-04-01

    The profile of brain structural abnormalities in schizophrenia is still not fully understood, despite decades of research using brain scans. To validate a prospective meta-analysis approach to analyzing multicenter neuroimaging data, we analyzed brain MRI scans from 2028 schizophrenia patients and 2540 healthy controls, assessed with standardized methods at 15 centers worldwide. We identified subcortical brain volumes that differentiated patients from controls, and ranked them according to their effect sizes. Compared with healthy controls, patients with schizophrenia had smaller hippocampus (Cohen's d=-0.46), amygdala (d=-0.31), thalamus (d=-0.31), accumbens (d=-0.25) and intracranial volumes (d=-0.12), as well as larger pallidum (d=0.21) and lateral ventricle volumes (d=0.37). Putamen and pallidum volume augmentations were positively associated with duration of illness and hippocampal deficits scaled with the proportion of unmedicated patients. Worldwide cooperative analyses of brain imaging data support a profile of subcortical abnormalities in schizophrenia, which is consistent with that based on traditional meta-analytic approaches. This first ENIGMA Schizophrenia Working Group study validates that collaborative data analyses can readily be used across brain phenotypes and disorders and encourages analysis and data sharing efforts to further our understanding of severe mental illness.

  17. The 'resting-state hypothesis' of major depressive disorder-a translational subcortical-cortical framework for a system disorder.

    PubMed

    Northoff, Georg; Wiebking, Christine; Feinberg, Todd; Panksepp, Jaak

    2011-10-01

    Major depressive disorder (MDD) has traditionally been characterized by various psychological symptoms, involvement of diverse functional systems (e.g., somatic, affect, cognition, reward, etc.), and with progress in neuroscience, an increasing number of brain regions. This has led to the general assumption that MDD is a stress-responsive brain 'system disorder' where either one or several alterations infiltrate a large number of functional systems in the brain that control the organism's somatic, affective, and cognitive life. However, while the effects or consequences of the abnormal changes in the functional systems of, for instance affect, cognition or reward have been investigated extensively, the underlying core mechanism(s) underlying MDD remain unknown. Hypotheses are proliferating rapidly, though. Based on recent findings, we will entertain an abnormality in the resting-state activity in MDD to be a core feature. Based on both animal and human data, we hypothesize that abnormal resting-state activity levels may impact stimulus-induced neural activity in medially situated core systems for self-representation as well as external stimulus (especially stress, specifically separation distress) interactions. Moreover, due to nested hierarchy between subcortical and cortical regions, we assume 'highjacking' of higher cortical affective and cognitive functions by lower subcortical primary-process emotional systems. This may account for the predominance of negative affect in somatic and cognitive functional system operations with the consecutive generation of the diverse symptoms in MDD. We will here focus on the neuroanatomical and biochemical basis of resting-state abnormalities in MDD including their linkage to the diverse psychopathological symptoms in depression. However, our 'resting-state hypothesis' may go well beyond that by being sufficiently precise to be linked to genetic, social, immunological, and endocrine dimensions and hypotheses as well as to

  18. The re-expression of the epigenetically silenced e-cadherin gene by a polyamine analogue lysine-specific demethylase-1 (LSD1) inhibitor in human acute myeloid leukemia cell lines

    PubMed Central

    Murray-Stewart, Tracy; Woster, Patrick M.; Casero, Robert A.

    2013-01-01

    Aberrant epigenetic silencing of tumor suppressor genes is a common feature observed during the transformation process of many cancers, including those of hematologic origin. Histone modifications, including acetylation, phosphorylation, and methylation, collaborate with DNA CpG island methylation to regulate gene expression. The dynamic process of histone methylation is the latest of these epigenetic modifications to be described, and the identification and characterization of LSD1 as a demethylase of lysine 4 of histone H3 (H3K4) has confirmed that both the enzyme and the modified histone play important roles as regulators of gene expression. LSD1 activity contributes to the suppression of gene expression by demethylating promoter-region mono- and dimethyl- H3K4 histone marks that are associated with active gene expression. As most posttranslational modifications are reversible, the enzymes involved in the modification of histones have become targets for chemotherapeutic intervention. In this study, we examined the effects of the polyamine analogue LSD1 inhibitor 2d (1,15-bis{N5-[3,3-(diphenyl)propyl]-N1-biguanido}-4,12-diazapentadecane) in human acute myeloid leukemia (AML) cell lines. In each line studied, 2d evoked cytotoxicity and inhibited LSD1 activity, as evidenced by increases in the global levels of mono- and di-methylated H3K4 proteins. Global increases in other chromatin modifications were also observed following exposure to 2d, suggesting a broad response to this compound with respect to chromatin regulation. On a gene-specific level, treatment with 2d resulted in the reexpression of e-cadherin, a tumor suppressor gene frequently silenced by epigenetic modification in AML. Quantitative chromatin immunoprecipitation analysis of the ecadherin promoter further confirmed that this re-expression was concurrent with changes in both active and repressive histone marks that were consistent with LSD1 inhibition. As hematologic malignancies have demonstrated

  19. Brief Screening of Vascular Cognitive Impairment in Patients With Cerebral Autosomal-Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy Without Dementia

    PubMed Central

    Hollocks, Matthew J.; Tan, Rhea Y.Y.; Morris, Robin G.; Markus, Hugh S.

    2016-01-01

    Background and Purpose— Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a monogenic form of cerebral small vessel disease leading to early-onset stroke and dementia, with younger patients frequently showing subclinical deficits in cognition. At present, there are no targeted cognitive screening measures for this population. However, the Brief Memory and Executive Test (BMET) and the Montreal Cognitive Assessment (MoCA) have shown utility in detecting cognitive impairment in sporadic small vessel disease. This study assesses the BMET and the MoCA as clinical tools for detecting mild cognitive deficits in CADASIL. Methods— Sixty-six prospectively recruited patients with CADASIL, and 66 matched controls completed the BMET, with a subset of these also completing the MoCA. Receiver operating characteristic curves were calculated to examine the sensitivity and specificity of clinical cutoffs for the detection of vascular cognitive impairment and reduced activities of daily living. Results— Patients with CADASIL showed more cognitive impairment overall and were poorer on both executive/processing and memory indices of the BMET relative to controls. The BMET showed good accuracy in predicting vascular cognitive impairment (85% sensitivity and 84% specificity) and impaired instrumental activities of daily living (92% sensitivity and 77% specificity). The MoCA also showed good predictive validity for vascular cognitive impairment (80% sensitivity and 78% specificity) and instrumental activities of daily living (75% sensitivity and 76% specificity). The most important background predictor of vascular cognitive impairment was a history of stroke. Conclusions— The results indicate that the BMET and the MoCA are clinically useful and sensitive screening measures for early cognitive impairment in patients with CADASIL. PMID:27625375

  20. A system for recording neural activity chronically and simultaneously from multiple cortical and subcortical regions in nonhuman primates

    PubMed Central

    Feingold, Joseph; Desrochers, Theresa M.; Fujii, Naotaka; Harlan, Ray; Tierney, Patrick L.; Shimazu, Hideki; Amemori, Ken-ichi

    2012-01-01

    A major goal of neuroscience is to understand the functions of networks of neurons in cognition and behavior. Recent work has focused on implanting arrays of ∼100 immovable electrodes or smaller numbers of individually adjustable electrodes, designed to target a few cortical areas. We have developed a recording system that allows the independent movement of hundreds of electrodes chronically implanted in several cortical and subcortical structures. We have tested this system in macaque monkeys, recording simultaneously from up to 127 electrodes in 14 brain regions for up to one year at a time. A key advantage of the system is that it can be used to sample different combinations of sites over prolonged periods, generating multiple snapshots of network activity from a single implant. Used in conjunction with microstimulation and injection methods, this versatile system represents a powerful tool for studying neural network activity in the primate brain. PMID:22170970

  1. Megalencephalic leukoencephalopathy with subcortical cysts: chronic white matter oedema due to a defect in brain ion and water homoeostasis.

    PubMed

    van der Knaap, Marjo S; Boor, Ilja; Estévez, Raúl

    2012-11-01

    Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is characterised by chronic white matter oedema. The disease has an infantile onset and leads to slow neurological deterioration in most cases, but, surprisingly, some patients recover. The first disease gene, MLC1, identified in 2001, is mutated in 75% of patients. At that time, nothing was known about MLC1 protein function and the pathophysiology of MLC. More recently, HEPACAM (also called GLIALCAM) has been identified as a second disease gene. GlialCAM serves as an escort for MLC1 and the chloride channel CLC2. The defect in MLC1 has been shown to hamper the cell volume regulation of astrocytes. One of the most important consequences involves the potassium siphoning process, which is essential in brain ion and water homoeostasis. An understanding of the mechanisms of white matter oedema in MLC is emerging. Further insight into the specific function of MLC1 is necessary to find treatment targets.

  2. The first Indian-origin family with genetically proven cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).

    PubMed

    Yadav, Sunaina; Bentley, Paul; Srivastava, Padma; Prasad, Kameshwar; Sharma, Pankaj

    2013-01-01

    We report the first family of Indian origin known to be affected by cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Seventeen members of the family spanning 3 generations had neurologic syndromes compatible with CADASIL, of whom 5 were genetically confirmed carriers of the Notch3 gene R141C mutation in exon 4 (421(C→T) and 141(Cys→Arg)). Our report highlights that CADASIL not only occurs sporadically in South Asians, but also may account for stroke in South Asians with a strong family history. Furthermore, the similarity of clinical presentations described here to those typical for Caucasian case series suggests that the CADASIL phenotype is preserved across racial groups.

  3. Extensive Direct Subcortical Cerebellum-Basal Ganglia Connections in Human Brain as Revealed by Constrained Spherical Deconvolution Tractography

    PubMed Central

    Milardi, Demetrio; Arrigo, Alessandro; Anastasi, Giuseppe; Cacciola, Alberto; Marino, Silvia; Mormina, Enricomaria; Calamuneri, Alessandro; Bruschetta, Daniele; Cutroneo, Giuseppina; Trimarchi, Fabio; Quartarone, Angelo

    2016-01-01

    The connections between the cerebellum and basal ganglia were assumed to occur at the level of neocortex. However evidences from animal data have challenged this old perspective showing extensive subcortical pathways linking the cerebellum with the basal ganglia. Here we tested the hypothesis if these connections also exist between the cerebellum and basal ganglia in the human brain by using diffusion magnetic resonance imaging and tractography. Fifteen healthy subjects were analyzed by using constrained spherical deconvolution technique obtained with a 3T magnetic resonance imaging scanner. We found extensive connections running between the subthalamic nucleus and cerebellar cortex and, as novel result, we demonstrated a direct route linking the dentate nucleus to the internal globus pallidus as well as to the substantia nigra. These findings may open a new scenario on the interpretation of basal ganglia disorders. PMID:27047348

  4. Frontal-subcortical circuitry in social attachment and relationships: A cross-sectional fMRI ALE meta-analysis.

    PubMed

    Lee, Shu-Hui; Walker, Zachary M; Hale, James B; Chen, S H Annabel

    2017-02-22

    Researchers have explored the concept of attachment in multiple ways, from animal studies examining imprinting to abnormal attachment in psychopathology. However, until recently, few have considered how neural circuitry develops the effective social bonds that are subsequently replicated in relationships across the lifespan. This current cross-sectional study undertook a fMRI Activation Likelihood Estimation (ALE) meta-analyses to examine the neurocircuitry that governs emotional and behavioural functions critical for building effective social relationships in children and adults. Results suggest that dissociable dorsal cognitive ("cool") and ventral - affective ("hot") frontal-subcortical circuits (FSC) work together to govern social relationships, with repeated social consequences leading to potentially adaptive - or maladaptive - relationships that can become routinized in the cerebellum. Implications for forming stable, functional, social bonds are considered, followed by recommendations for those who struggle with cool and hot FSC functioning that can hinder the development of adaptive prosocial relationships.

  5. Alzheimer’s disease—subcortical vascular disease spectrum in a hospital-based setting: Overview of results from the Gothenburg MCI and dementia studies

    PubMed Central

    Nordlund, Arto; Jonsson, Michael; Blennow, Kaj; Zetterberg, Henrik; Öhrfelt, Annika; Stålhammar, Jacob; Eckerström, Marie; Carlsson, Mårten; Olsson, Erik; Göthlin, Mattias; Svensson, Johan; Rolstad, Sindre; Eckerström, Carl; Bjerke, Maria

    2016-01-01

    The ability to discriminate between Alzheimer’s disease (AD), subcortical vascular disease, and other cognitive disorders is crucial for diagnostic purposes and clinical trial outcomes. Patients with primarily subcortical vascular disease are unlikely to benefit from treatments targeting the AD pathogenic mechanisms and vice versa. The Gothenburg mild cognitive impairment (MCI) and dementia studies are prospective, observational, single-center cohort studies suitable for both cross-sectional and longitudinal analysis that outline the cognitive profiles and biomarker characteristics of patients with AD, subcortical vascular disease, and other cognitive disorders. The studies, the first of which started in 1987, comprise inpatients with manifest dementia and patients seeking care for cognitive disorders at an outpatient memory clinic. This article gives an overview of the major published papers (neuropsychological, imaging/physiology, and neurochemical) of the studies including the ongoing Gothenburg MCI study. The main findings suggest that subcortical vascular disease with or without dementia exhibit a characteristic neuropsychological pattern of mental slowness and executive dysfunction and neurochemical deviations typical of white matter changes and disturbed blood–brain barrier function. Our findings may contribute to better healthcare for this underrecognized group of patients. The Gothenburg MCI study has also published papers on multimodal prediction of dementia, and cognitive reserve. PMID:26219595

  6. The processing of lexical ambiguity in healthy ageing and Parkinson׳s disease: role of cortico-subcortical networks.

    PubMed

    Ketteler, Simon; Ketteler, Daniel; Vohn, René; Kastrau, Frank; Schulz, Jörg B; Reetz, Kathrin; Huber, Walter

    2014-09-18

    Previous neuroimaging studies showed that correct resolution of lexical ambiguity relies on the integrity of prefrontal and inferior parietal cortices. Whereas prefrontal brain areas were associated with executive control over semantic selection, inferior parietal areas were linked with access to modality-independent representations of semantic memory. Yet insufficiently understood is the contribution of subcortical structures in ambiguity processing. Patients with disturbed basal ganglia function such as Parkinson׳s disease (PD) showed development of discourse comprehension deficits evoked by lexical ambiguity. To further investigate the engagement of cortico-subcortical networks functional Magnetic Resonance Imaging (fMRI) was monitored during ambiguity resolution in eight early PD patients without dementia and 14 age- and education-matched controls. Participants were required to relate meanings to a lexically ambiguous target (homonym). Each stimulus consisted of two words arranged on top of a screen, which had to be attributed to a homonym at the bottom. Brain activity was found in bilateral inferior parietal (BA 39), right middle temporal (BA 21/22), left middle frontal (BA 10) and bilateral inferior frontal areas (BA 45/46). Extent and amplitude of activity in the angular gyrus changed depending on semantic association strength that varied between conditions. Less activity in the left caudate was associated with semantic integration deficits in PD. The results of the present study suggest a relationship between subtle language deficits and early stages of basal ganglia dysfunction. Uncovering impairments in ambiguity resolution may be of future use in the neuropsychological assessment of non-motor deficits in PD.

  7. The Spanish version of the Addenbrooke's Cognitive Examination - Revised (ACE-R) in subcortical ischemic vascular dementia.

    PubMed

    Raimondi, Catalina; Gleichgerrcht, Ezequiel; Richly, Pablo; Torralva, Teresa; Roca, María; Camino, Julieta; Manes, Facundo

    2012-11-15

    Vascular dementia (VaD) is one of the most prevalent causes of dementia, and it is frequently misdiagnosed and undertreated in clinical practice. Because neuropsychological outcome depends, among other factors, on the size and location of the vascular brain injury, characterizing the cognitive profile of VaD has been especially challenging. Yet, there has been sufficient evidence to show a marked impairment of attention and executive functions, in particular in relation to Alzheimer disease. Being able to detect these deficits at bedside is crucial for everyday clinical practice, and yet, brief cognitive screening toots such as the Mini-Mental Sate Examination (MMSE) may overlook at cognitive deficits typical of patients with VaD. The Addenbrooke's Cognitive Examination Revised (ACE-R) is also a brief cognitive screening tool designed to incorporate the items of the MMSE and further extend the test to assess orientation, attention, verbal fluency, memory, language, and visuospatial abilities. In this study, we investigated the ability of the Spanish version of the ACE-R to detect the cognitive impairment showed in patients with subcortical ischemic vascular dementia, and we compared its usefulness to that of the MMSE in this population. Scores on these tests were compared to those of patients with Alzheimer disease and matched healthy controls. The 88-point cut-off proposed for the ACE-R was associated with a sensitivity of 100% and a specificity of 100% for the detection of cognitive impairment, demonstrating a stronger capacity than the MMSE (sensitivity of 42% with its 23-point cut-off score). We also found that the verbal fluency subtest of the ACE-R may be potentially useful in discriminating patients with subcortical ischemic vascular dementia from patients with AD. We discuss the utility of these findings in the context of everyday clinical practice and we propose that future studies should evaluate the potential usefulness of combining the ACE-R with a

  8. Power spectral analysis of EEG activity obtained from cortical and subcortical sites during the vigilance states of the cat.

    PubMed

    Bronzino, J D; Stern, W C; Leahy, J P; Morgane, P J

    1976-01-01

    There is considerable evidence that the raphé system and the region of the nucleus tractus solitarious (NTS), including the area postrema, play significant roles in slow-wave sleep mechanisms and in EEG synchronization. Studies of the interactions between these systems and the neocortex are much needed. If neuronal activity in these lower brainstem regions regulates the degree of cortical synchrony then a high degree of correspondence between the EEG of the area postrema or raphé complex with that of the cortex might be expected. In order to quantitate the reequency characteristics of the EEG obtained from these subcortical sites (nucleus raphé dorsalis, area postrema, as well as anatomical controls adjacent to these regions) during the different vigilance states (waking, slow-wave sleep, REM sleep) in the cat, power spectral analyses techniques were employed. Comparison of these subcortical spectral characteristic with those obtained from cortical (frontal and occipital) sites during the same vigilance state, show that the spectral measures elicited from the region of the area postrema closely correspond to that of the cortex, particularly during slow-wave sleep. On the other hand, the EEG of the anterior portion of the raphé region, although exhibiting a substantial low frequency component during slow-wave sleep in comparison to wakefulness does not show a statistically significant shift to low frequencies such as occurs in the area postrema or the cortex. These results suggest that the increases in the low frequency content of the cortical EEG sites during slow-wave sleep results from synchronizing inputs from the area postrema to a greater extent than from the raphé complex.

  9. From Cortical and Subcortical Grey Matter Abnormalities to Neurobehavioral Phenotype of Angelman Syndrome: A Voxel-Based Morphometry Study

    PubMed Central

    Aghakhanyan, Gayane; Bonanni, Paolo; Randazzo, Giovanna; Nappi, Sara; Tessarotto, Federica; De Martin, Lara; Frijia, Francesca; De Marchi, Daniele; De Masi, Francesco; Kuppers, Beate; Lombardo, Francesco; Caramella, Davide; Montanaro, Domenico

    2016-01-01

    Angelman syndrome (AS) is a rare neurogenetic disorder due to loss of expression of maternal ubiquitin-protein ligase E3A (UBE3A) gene. It is characterized by severe developmental delay, speech impairment, movement or balance disorder and typical behavioral uniqueness. Affected individuals show normal magnetic resonance imaging (MRI) findings, although mild dysmyelination may be observed. In this study, we adopted a quantitative MRI analysis with voxel-based morphometry (FSL-VBM) method to investigate disease-related changes in the cortical/subcortical grey matter (GM) structures. Since 2006 to 2013 twenty-six AS patients were assessed by our multidisciplinary team. From those, sixteen AS children with confirmed maternal 15q11-q13 deletions (mean age 7.7 ± 3.6 years) and twenty-one age-matched controls were recruited. The developmental delay and motor dysfunction were assessed using Bayley III and Gross Motor Function Measure (GMFM). Principal component analysis (PCA) was applied to the clinical and neuropsychological datasets. High-resolution T1-weighted images were acquired and FSL-VBM approach was applied to investigate differences in the local GM volume and to correlate clinical and neuropsychological changes in the regional distribution of GM. We found bilateral GM volume loss in AS compared to control children in the striatum, limbic structures, insular and orbitofrontal cortices. Voxel-wise correlation analysis with the principal components of the PCA output revealed a strong relationship with GM volume in the superior parietal lobule and precuneus on the left hemisphere. The anatomical distribution of cortical/subcortical GM changes plausibly related to several clinical features of the disease and may provide an important morphological underpinning for clinical and neurobehavioral symptoms in children with AS. PMID:27626634

  10. Auditory processing in schizophrenia during the middle latency period (10–50 ms): high-density electrical mapping and source analysis reveal subcortical antecedents to early cortical deficits

    PubMed Central

    Leavitt, Victoria M.; Molholm, Sophie; Ritter, Walter; Shpaner, Marina; Foxe, John J.

    2007-01-01

    Introduction Auditory sensory processing dysfunction is a core component of schizophrenia, with deficits occurring at 50 ms post-stimulus firmly established in the literature. Given that the initial afference of primary auditory cortex occurs at least 35 ms earlier, however, an essential question remains: how early in sensory processing do such deficits arise, and do they occur during initial cortical afference or earlier, which would implicate subcortical auditory dysfunction. Objective To establish the onset of the earliest deficits in auditory processing, we examined the time window demarcating the transition from subcortical to cortical processing: 10 ms to 50 ms during the so-called middle latency responses (MLRs). These remain to be adequately characterized in patients with schizophrenia. Methods We recorded auditory evoked potentials (AEPs) to simple tone-pips from 15 control subjects and 21 medicated patients with longer-term schizophrenia or schizoaffective disorder (illness duration 16 yr, standard deviation [SD] 9.4 yr), using high-density electrical scalp recordings. Between-group analyses assessed the integrity of the MLRs across groups. In addition, 2 source-localization models were conducted to address whether a distinction between subcortical and cortical generators of the MLRs can be made and whether evidence for differential dorsal and ventral pathway contributions to auditory processing deficits can be established. Results Robust auditory processing deficits were found for patients as early as 15 ms. Evidence for subcortical generators of the earliest MLR component (P20) was provided by source analysis. Topographical mapping and source localization also pointed to greater decrements in processing in the dorsal auditory pathway of patients, providing support for a theory of pervasive deficits that are organized along the lines of a dorsal–ventral distinction. Conclusions Auditory sensory dysfunction in schizophrenia begins extremely early in

  11. Subcortical oligodendrocyte- and astrocyte-associated gene expression in subjects with schizophrenia, major depression and bipolar disorder.

    PubMed

    Barley, Kevin; Dracheva, Stella; Byne, William

    2009-07-01

    Deficits in the expression of oligodendrocyte and myelin genes have been described in numerous cortical regions in schizophrenia and affective disorders; however, relatively little attention has been paid to subcortical structures. Here we employed quantitative real time PCR to examine the mRNA expression of 17 genes that are expressed by oligodendrocyte precursors (OLPs) and their derivatives, including astrocytes. Four subcortical regions were examined (the anteroventral (AV) and mediodorsal thalamic nuclei (MDN), internal capsule (IC) and putamen (Put)) in postmortem material from subjects (age 25-68 at time of death) with no known psychiatric history (NCs) as well as in subjects with schizophrenia (SZ), major depressive disorder (MDD), and bipolar disorder (BPD). In all regions examined, genes expressed after the terminal differentiation of oligodendrocytes tended to have lower levels of mRNA expression in subjects with SZ compared to NCs. These differences were statistically significant across regions for four genes (CNP, GALC, MAG and MOG) and approached significance for TF. No genes were under expressed in MDD. Only TF was under expressed in BPD and only in the IC. In contrast, two astrocyte-associated genes (GFAP and ALDH1L1) had higher mean expression levels across regions in all psychiatric groups relative to NCs. These differences reached statistical significance for SZ and MDD relative to NCs. There were no age by diagnosis interactions. The majority of age regressions had negative slopes for the expression of oligodendrocyte-associated genes. GFAP but not ALDH1L1 expression was significantly and positively correlated with age in the MDN, AV and Put. Across subject groups the expression of both astrocyte genes was highly correlated with cumulative neuroleptic exposure in all regions except the Put. Significant positive correlations were also observed in some regions between cumulative neuroleptic exposure and the expression of genes associated with

  12. Neural Correlates for Apathy: Frontal-Prefrontal and Parietal Cortical- Subcortical Circuits.

    PubMed

    Moretti, Rita; Signori, Riccardo

    2016-01-01

    Apathy is an uncertain nosographical entity, which includes reduced motivation, abulia, decreased empathy, and lack of emotional involvement; it is an important and heavy-burden clinical condition which strongly impacts in everyday life events, affects the common daily living abilities, reduced the inner goal directed behavior, and gives the heaviest burden on caregivers. Is a quite common comorbidity of many neurological disease, However, there is no definite consensus on the role of apathy in clinical practice, no definite data on anatomical circuits involved in its development, and no definite instrument to detect it at bedside. As a general observation, the occurrence of apathy is connected to damage of prefrontal cortex (PFC) and basal ganglia; "emotional affective" apathy may be related to the orbitomedial PFC and ventral striatum; "cognitive apathy" may be associated with dysfunction of lateral PFC and dorsal caudate nuclei; deficit of "autoactivation" may be due to bilateral lesions of the internal portion of globus pallidus, bilateral paramedian thalamic lesions, or the dorsomedial portion of PFC. On the other hand, apathy severity has been connected to neurofibrillary tangles density in the anterior cingulate gyrus and to gray matter atrophy in the anterior cingulate (ACC) and in the left medial frontal cortex, confirmed by functional imaging studies. These neural networks are linked to projects, judjing and planning, execution and selection common actions, and through the basolateral amygdala and nucleus accumbens projects to the frontostriatal and to the dorsolateral prefrontal cortex. Therefore, an alteration of these circuitry caused a lack of insight, a reduction of decision-making strategies, and a reduced speedness in action decision, major responsible for apathy. Emergent role concerns also the parietal cortex, with its direct action motivation control. We will discuss the importance of these circuits in different pathologies, degenerative or

  13. Neural Correlates for Apathy: Frontal-Prefrontal and Parietal Cortical- Subcortical Circuits

    PubMed Central

    Moretti, Rita; Signori, Riccardo

    2016-01-01

    Apathy is an uncertain nosographical entity, which includes reduced motivation, abulia, decreased empathy, and lack of emotional involvement; it is an important and heavy-burden clinical condition which strongly impacts in everyday life events, affects the common daily living abilities, reduced the inner goal directed behavior, and gives the heaviest burden on caregivers. Is a quite common comorbidity of many neurological disease, However, there is no definite consensus on the role of apathy in clinical practice, no definite data on anatomical circuits involved in its development, and no definite instrument to detect it at bedside. As a general observation, the occurrence of apathy is connected to damage of prefrontal cortex (PFC) and basal ganglia; “emotional affective” apathy may be related to the orbitomedial PFC and ventral striatum; “cognitive apathy” may be associated with dysfunction of lateral PFC and dorsal caudate nuclei; deficit of “autoactivation” may be due to bilateral lesions of the internal portion of globus pallidus, bilateral paramedian thalamic lesions, or the dorsomedial portion of PFC. On the other hand, apathy severity has been connected to neurofibrillary tangles density in the anterior cingulate gyrus and to gray matter atrophy in the anterior cingulate (ACC) and in the left medial frontal cortex, confirmed by functional imaging studies. These neural networks are linked to projects, judjing and planning, execution and selection common actions, and through the basolateral amygdala and nucleus accumbens projects to the frontostriatal and to the dorsolateral prefrontal cortex. Therefore, an alteration of these circuitry caused a lack of insight, a reduction of decision-making strategies, and a reduced speedness in action decision, major responsible for apathy. Emergent role concerns also the parietal cortex, with its direct action motivation control. We will discuss the importance of these circuits in different pathologies

  14. Grapheme-color synesthetes show peculiarities in their emotional brain: cortical and subcortical evidence from VBM analysis of 3D-T1 and DTI data.

    PubMed

    Melero, Helena; Peña-Melián, Ángel; Ríos-Lago, Marcos; Pajares, Gonzalo; Hernández-Tamames, Juan Antonio; Álvarez-Linera, Juan

    2013-06-01

    Grapheme-color synesthesia is a neurological phenomenon in which viewing achromatic letters/numbers leads to automatic and involuntary color experiences. In this study, voxel-based morphometry analyses were performed on T1 images and fractional anisotropy measures to examine the whole brain in associator grapheme-color synesthetes. These analyses provide new evidence of variations in emotional areas (both at the cortical and subcortical levels), findings that help understand the emotional component as a relevant aspect of the synesthetic experience. Additionally, this study replicates previous findings in the left intraparietal sulcus and, for the first time, reports the existence of anatomical differences in subcortical gray nuclei of developmental grapheme-color synesthetes, providing a link between acquired and developmental synesthesia. This empirical evidence, which goes beyond modality-specific areas, could lead to a better understanding of grapheme-color synesthesia as well as of other modalities of the phenomenon.

  15. A novel Notch3 deletion mutation in a Chinese patient with cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL).

    PubMed

    Weiming, Fan; Yuliang, Wang; Youjie, Li; Xinsheng, Liu; Shuyang, Xie; Zhaoxia, Liu

    2013-02-01

    Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) is a rare autosomal dominant hereditary cerebrovascular disease characterised by migraine attacks, recurrent subcortical transient ischemic attacks or strokes, cognitive decline, and dementia. It is caused by mutations in the Notch3 gene on chromosome 19p13.1, which is the only gene currently known to be closely associated with CADASIL. We describe a novel 100 base pair base fragment deletion mutation (ENST 00000263388, c.512-611del) in the Notch3 gene from a Chinese patient with CADASIL. The present patient has the characteristic clinical and family history for CADASIL, which suggests that C.512del611 may be a cause of CADASIL as well as most of the previously reported Notch3 mutations.

  16. Megalencephalic leukoencephalopathy with subcortical cysts protein 1 regulates glial surface localization of GLIALCAM from fish to humans.

    PubMed

    Sirisi, Sònia; Folgueira, Mónica; López-Hernández, Tania; Minieri, Laura; Pérez-Rius, Carla; Gaitán-Peñas, Héctor; Zang, Jingjing; Martínez, Albert; Capdevila-Nortes, Xavier; De La Villa, Pedro; Roy, Upasana; Alia, A; Neuhauss, Stephan; Ferroni, Stefano; Nunes, Virginia; Estévez, Raúl; Barrallo-Gimeno, Alejandro

    2014-10-01

    Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a leukodystrophy characterized by myelin vacuolization and caused by mutations in MLC1 or GLIALCAM. Patients with recessive mutations in either MLC1 or GLIALCAM show the same clinical phenotype. It has been shown that GLIALCAM is necessary for the correct targeting of MLC1 to the membrane at cell junctions, but its own localization was independent of MLC1 in vitro. However, recent studies in Mlc1(-/-) mice have shown that GlialCAM is mislocalized in glial cells. In order to investigate whether the relationship between Mlc1 and GlialCAM is species-specific, we first identified MLC-related genes in zebrafish and generated an mlc1(-/-) zebrafish. We have characterized mlc1(-/-) zebrafish both functionally and histologically and compared the phenotype with that of the Mlc1(-/-) mice. In mlc1(-/-) zebrafish, as in Mlc1(-/-) mice, Glialcam is mislocalized. Re-examination of a brain biopsy from an MLC patient indicates that GLIALCAM is also mislocalized in Bergmann glia in the cerebellum. In vitro, impaired localization of GlialCAM was observed in astrocyte cultures from Mlc1(-/-) mouse only in the presence of elevated potassium levels, which mimics neuronal activity. In summary, here we demonstrate an evolutionary conserved role for MLC1 in regulating glial surface levels of GLIALCAM, and this interrelationship explains why patients with mutations in either gene (MLC1 or GLIALCAM) share the same clinical phenotype.

  17. Relative activity of cerebral subcortical gray matter in varying states of attention and awareness in normal subjects and patient studies

    SciTech Connect

    Cooper, M.; Chen, C.T.; Levy, J.; Wagner, N.; Spire, J.P.; Jacobsen, J.; Meltzer, H.; Metz, J.; Beck, R.N.

    1985-05-01

    An important aspect of the study of brain function involves measurement of the relationships; between activities in the subcortical gray matter of the caudate and of the thalamus; and between these structures and functional cortical areas. The authors have studied these relationships in 22 subjects under different conditions of activation, sleep and sensory deprivation using a PET VI system and F-18-2DG to determine regional cerebral metabolism. Subject activating conditions were maintained throughout the period of equilibration of F-18-2DG and E.E.G.'s were monitored. Multiple tomographic slices of 1-2 million counts were obtained simultaneously with slice separation of 14mm and each plane parallel to the cantho-meatal line. In activated and non-activated awake conditions for normal subjects, left and right thalmus-to-caudate ratios were similar and greater than unity. This relationship was maintained in non-REM sleep, but was reversed and divergent in REM sleep and sensory deprivation; this was also evident in 3/4 narcoleptics awake and asleep in non-REM and REM and 2/3 schizophrenics and affective disorder, subjects. This approach appears to have potential for characterizating normal and disordered regional cerebral function.

  18. Evidence for a Role of a Cortico-Subcortical Network for Automatic and Unconscious Motor Inhibition of Manual Responses

    PubMed Central

    D’Ostilio, Kevin; Collette, Fabienne; Phillips, Christophe; Garraux, Gaëtan

    2012-01-01

    It is now clear that non-consciously perceived stimuli can bias our decisions. Although previous researches highlighted the importance of automatic and unconscious processes involved in voluntary action, the neural correlates of such processes remain unclear. Basal ganglia dysfunctions have long been associated with impairment in automatic motor control. In addition, a key role of the medial frontal cortex has been suggested by administrating a subliminal masked prime task to a patient with a small lesion restricted to the supplementary motor area (SMA). In this task, invisible masked arrows stimuli were followed by visible arrow targets for a left or right hand response at different interstimuli intervals (ISI), producing a traditional facilitation effect for compatible trials at short ISI and a reversal inhibitory effect at longer ISI. Here, by using fast event-related fMRI and a weighted parametric analysis, we showed BOLD related activity changes in a cortico-subcortical network, especially in the SMA and the striatum, directly linked to the individual behavioral pattern. This new imaging result corroborates previous works on subliminal priming using lesional approaches. This finding implies that one of the roles of these regions was to suppress a partially activated movement below the threshold of awareness. PMID:23110158

  19. The Role of Anterior Nuclei of the Thalamus: A Subcortical Gate in Memory Processing: An Intracerebral Recording Study

    PubMed Central

    Štillová, Klára; Jurák, Pavel; Chládek, Jan; Chrastina, Jan; Halámek, Josef; Bočková, Martina; Goldemundová, Sabina; Říha, Ivo; Rektor, Ivan

    2015-01-01

    Objective To study the involvement of the anterior nuclei of the thalamus (ANT) as compared to the involvement of the hippocampus in the processes of encoding and recognition during visual and verbal memory tasks. Methods We studied intracerebral recordings in patients with pharmacoresistent epilepsy who underwent deep brain stimulation (DBS) of the ANT with depth electrodes implanted bilaterally in the ANT and compared the results with epilepsy surgery candidates with depth electrodes implanted bilaterally in the hippocampus. We recorded the event-related potentials (ERPs) elicited by the visual and verbal memory encoding and recognition tasks. Results P300-like potentials were recorded in the hippocampus by visual and verbal memory encoding and recognition tasks and in the ANT by the visual encoding and visual and verbal recognition tasks. No significant ERPs were recorded during the verbal encoding task in the ANT. In the visual and verbal recognition tasks, the P300-like potentials in the ANT preceded the P300-like potentials in the hippocampus. Conclusions The ANT is a structure in the memory pathway that processes memory information before the hippocampus. We suggest that the ANT has a specific role in memory processes, especially memory recognition, and that memory disturbance should be considered in patients with ANT-DBS and in patients with ANT lesions. ANT is well positioned to serve as a subcortical gate for memory processing in cortical structures. PMID:26529407

  20. Shape abnormalities of subcortical and ventricular structures in mild cognitive impairment and Alzheimer's disease: detecting, quantifying, and predicting.

    PubMed

    Tang, Xiaoying; Holland, Dominic; Dale, Anders M; Younes, Laurent; Miller, Michael I

    2014-08-01

    This article assesses the feasibility of using shape information to detect and quantify the subcortical and ventricular structural changes in mild cognitive impairment (MCI) and Alzheimer's disease (AD) patients. We first demonstrate structural shape abnormalities in MCI and AD as compared with healthy controls (HC). Exploring the development to AD, we then divide the MCI participants into two subgroups based on longitudinal clinical information: (1) MCI patients who remained stable; (2) MCI patients who converted to AD over time. We focus on seven structures (amygdala, hippocampus, thalamus, caudate, putamen, globus pallidus, and lateral ventricles) in 754 MR scans (210 HC, 369 MCI of which 151 converted to AD over time, and 175 AD). The hippocampus and amygdala were further subsegmented based on high field 0.8 mm isotropic 7.0T scans for finer exploration. For MCI and AD, prominent ventricular expansions were detected and we found that these patients had strongest hippocampal atrophy occurring at CA1 and strongest amygdala atrophy at the basolateral complex. Mild atrophy in basal ganglia structures was also detected in MCI and AD. Stronger atrophy in the amygdala and hippocampus, and greater expansion in ventricles was observed in MCI converters, relative to those MCI who remained stable. Furthermore, we performed principal component analysis on a linear shape space of each structure. A subsequent linear discriminant analysis on the principal component values of hippocampus, amygdala, and ventricle leads to correct classification of 88% HC subjects and 86% AD subjects.

  1. Early constraint-induced movement therapy promotes functional recovery and neuronal plasticity in a subcortical hemorrhage model rat.

    PubMed

    Ishida, Akimasa; Misumi, Sachiyo; Ueda, Yoshitomo; Shimizu, Yuko; Cha-Gyun, Jung; Tamakoshi, Keigo; Ishida, Kazuto; Hida, Hideki

    2015-05-01

    Constraint-induced movement therapy (CIMT) promotes functional recovery of impaired forelimbs after hemiplegic strokes, including intracerebral hemorrhage (ICH). We used a rat model of subcortical hemorrhage to compare the effects of delivering early or late CIMT after ICH. The rat model was made by injecting collagenase into the globus pallidus near the internal capsule, and then forcing rats to use the affected forelimb for 7 days starting either 1 day (early CIMT) or 17 days (late CIMT) after the lesion. Recovery of forelimb function in the skilled reaching test and the ladder stepping test was found after early-CIMT, while no significant recovery was shown after late CIMT or in the non-CIMT controls. Early CIMT was associated with greater numbers of ΔFosB-positive cells in the ipsi-lesional sensorimotor cortex layers II-III and V. Additionally, we found expression of the growth-related genes brain-derived neurotrophic factor (BDNF) and growth-related protein 43 (GAP-43), and abundant dendritic arborization of pyramidal neurons in the sensorimotor area. Similar results were not detected in the contra-lesional cortex. In contrast to early CIMT, late CIMT failed to induce any changes in plasticity. We conclude that CIMT induces molecular and morphological plasticity in the ipsi-lesional sensorimotor cortex and facilitates better functional recovery when initiated immediately after hemorrhage.

  2. Diminution of the NMDA receptor NR2B subunit in cortical and subcortical areas of WAG/Rij rats.

    PubMed

    Karimzadeh, Fariba; Soleimani, Mansoureh; Mehdizadeh, Mehdi; Jafarian, Maryam; Mohamadpour, Maliheh; Kazemi, Hadi; Joghataei, Mohammad-Taghi; Gorji, Ali

    2013-12-01

    Modulation of glutamatergic NMDA receptors affects the synchronization of spike discharges in in WAG/Rij rats, a valid genetic animal model of absence epilepsy. In this study, we describe the alteration of NR2B subunit of NMDA receptors expression in WAG/Rij rats in different somatosensory cortical layers and in hippocampal CA1 area. Experimental groups were divided into four groups of six rats of both WAG/Rij and Wistar strains with 2 and 6 months of age. The distribution of NR2B receptors was assessed by immunohistochemical staining in WAG/Rij and compared with age-matched Wistar rats. The expression of NR2B subunit was significantly decreased in different somatosensory cortical layers in 2- and 6-month-old WAG/Rij rats. In addition, the distribution of NR2B in hippocampal CA1 area was lower in 6-month-old WAG/Rij compared with age-matched Wistar rats. The reduction of NR2B receptors in different brain areas points to disturbance of glutamate receptors expression in cortical and subcortical areas in WAG/Rij rats. An altered subunit assembly of NMDA receptors may underlie cortical hyperexcitability in absence epilepsy.

  3. Simultaneous EEG and fMRI reveals a causally connected subcortical-cortical network during reward anticipation.

    PubMed

    Plichta, Michael M; Wolf, Isabella; Hohmann, Sarah; Baumeister, Sarah; Boecker, Regina; Schwarz, Adam J; Zangl, Maria; Mier, Daniela; Diener, Carsten; Meyer, Patric; Holz, Nathalie; Ruf, Matthias; Gerchen, Martin F; Bernal-Casas, David; Kolev, Vasil; Yordanova, Juliana; Flor, Herta; Laucht, Manfred; Banaschewski, Tobias; Kirsch, Peter; Meyer-Lindenberg, Andreas; Brandeis, Daniel

    2013-09-04

    Electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) have been used to study the neural correlates of reward anticipation, but the interrelation of EEG and fMRI measures remains unknown. The goal of the present study was to investigate this relationship in response to a well established reward anticipation paradigm using simultaneous EEG-fMRI recording in healthy human subjects. Analysis of causal interactions between the thalamus (THAL), ventral-striatum (VS), and supplementary motor area (SMA), using both mediator analysis and dynamic causal modeling, revealed that (1) THAL fMRI blood oxygenation level-dependent (BOLD) activity is mediating intermodal correlations between the EEG contingent negative variation (CNV) signal and the fMRI BOLD signal in SMA and VS, (2) the underlying causal connectivity network consists of top-down regulation from SMA to VS and SMA to THAL along with an excitatory information flow through a THAL→VS→SMA route during reward anticipation, and (3) the EEG CNV signal is best predicted by a combination of THAL fMRI BOLD response and strength of top-down regulation from SMA to VS and SMA to THAL. Collectively, these findings represent a likely neurobiological mechanism mapping a primarily subcortical process, i.e., reward anticipation, onto a cortical signature.

  4. A Versatile Murine Model of Subcortical White Matter Stroke for the Study of Axonal Degeneration and White Matter Neurobiology.

    PubMed

    Nunez, Stefanie; Doroudchi, M Mehdi; Gleichman, Amy J; Ng, Kwan L; Llorente, Irene L; Sozmen, Elif G; Carmichael, S Thomas; Hinman, Jason D

    2016-03-17

    Stroke affecting white matter accounts for up to 25% of clinical stroke presentations, occurs silently at rates that may be 5-10 fold greater, and contributes significantly to the development of vascular dementia. Few models of focal white matter stroke exist and this lack of appropriate models has hampered understanding of the neurobiologic mechanisms involved in injury response and repair after this type of stroke. The main limitation of other subcortical stroke models is that they do not focally restrict the infarct to the white matter or have primarily been validated in non-murine species. This limits the ability to apply the wide variety of murine research tools to study the neurobiology of white matter stroke. Here we present a methodology for the reliable production of a focal stroke in murine white matter using a local injection of an irreversible eNOS inhibitor. We also present several variations on the general protocol including two unique stereotactic variations, retrograde neuronal tracing, as well as fresh tissue labeling and dissection that greatly expand the potential applications of this technique. These variations allow for multiple approaches to analyze the neurobiologic effects of this common and understudied form of stroke.

  5. A new neonatal cortical and subcortical brain atlas: the Melbourne Children's Regional Infant Brain (M-CRIB) atlas.

    PubMed

    Alexander, Bonnie; Murray, Andrea L; Loh, Wai Yen; Matthews, Lillian G; Adamson, Chris; Beare, Richard; Chen, Jian; Kelly, Claire E; Rees, Sandra; Warfield, Simon K; Anderson, Peter J; Doyle, Lex W; Spittle, Alicia J; Cheong, Jeanie L Y; Seal, Marc L; Thompson, Deanne K

    2017-02-15

    Investigating neonatal brain structure and function can offer valuable insights into behaviour and cognition in healthy and clinical populations; both at term age, and longitudinally in comparison with later time points. Parcellated brain atlases for adult populations are readily available, however warping infant data to adult template space is not ideal due to morphological and tissue differences between these groups. Several parcellated neonatal atlases have been developed, although there remains strong demand for manually parcellated ground truth data with detailed cortical definition. Additionally, compatibility with existing adult atlases is favourable for use in longitudinal investigations. We aimed to address these needs by replicating the widely-used Desikan-Killiany (2006) adult cortical atlas in neonates. We also aimed to extend brain coverage by complementing this cortical scheme with basal ganglia, thalamus, cerebellum and other subcortical segmentations. Thus, we have manually parcellated these areas volumetrically using high-resolution neonatal T2-weighted MRI scans, and initial automated and manually edited tissue classification, providing 100 regions in all. Linear and nonlinear T2-weighted structural templates were also generated. In this paper we provide manual parcellation protocols, and present the parcellated probability maps and structural templates together as the Melbourne Children's Regional Infant Brain (M-CRIB) atlas.

  6. On the role of suppression in spatial attention: evidence from negative BOLD in human subcortical and cortical structures.

    PubMed

    Gouws, André D; Alvarez, Ivan; Watson, David M; Uesaki, Maiko; Rodgers, Jessica; Rogers, Jessica; Morland, Antony B

    2014-07-30

    There is clear evidence that spatial attention increases neural responses to attended stimuli in extrastriate visual areas and, to a lesser degree, in earlier visual areas. Other evidence shows that neurons representing unattended locations can also be suppressed. However, the extent to which enhancement and suppression is observed, their stimulus dependence, and the stages of the visual system at which they are expressed remains poorly understood. Using fMRI we set out to characterize both the task and stimulus dependence of neural responses in the lateral geniculate nucleus (LGN), primary visual cortex (V1), and visual motion area (V5) in humans to determine where suppressive and facilitatory effects of spatial attention are expressed. Subjects viewed a lateralized drifting grating stimulus, presented at multiple stimulus contrasts, and performed one of three tasks designed to alter the spatial location of their attention. In retinotopic representations of the stimulus location, we observed increasing attention-dependent facilitation and decreasing dependence on stimulus contrast moving up the visual hierarchy from the LGN to V5. However, in the representations of unattended locations of the LGN and V1, we observed suppression, which was not significantly dependent on the attended stimulus contrast. These suppressive effects were also found in the pulvinar, which has been frequently associated with attention. We provide evidence, therefore, for a spatially selective suppressive mechanism that acts at a subcortical level.

  7. Microstructural White Matter Abnormalities and Cognitive Dysfunction in Subcortical Ischemic Vascular Disease: an Atlas-Based Diffusion Tensor Analysis Study.

    PubMed

    Lin, Lin; Xue, Yunjing; Duan, Qing; Sun, Bin; Lin, Hailong; Chen, Xiaodan; Luo, Ling; Wei, Xiaofan; Zhang, Zhongping

    2015-06-01

    Recent studies in subcortical ischemic vascular disease (SIVD) suggest the involvement of white matter (WM) abnormalities underlying the pathogenesis of cognitive function impairment. Here, we performed magnetic resonance diffusion tensor imaging (DTI) on detecting WM damage and to investigate the correlations between DTI measures and cognitive dysfunction in SIVD patients. Fifty right-handed SIVD patients were recruited and divided into vascular cognitive impairment on dementia (VCIND) group and normal cognition (NC) group. Twenty-two VCIND patients and 28 NC patients underwent DTI scanning and neuropsychological assessment. Atlas-based analysis (ABA) was performed on each subject for extracting FA and MD measures from supratentorial tracts. Among VCIND, as compared to NC patients, decreased FA and increased MD were observed in all projection fibers (bilateral anterior, posterior limb, and retrolenticular part of internal capsule, anterior, superior, and posterior corona radiata and posterior thalamic radiation), association fibers (bilateral sagittal stratum, external capsule, cingulum, fornix, and stria terminalis, superior longitudinal fasciculus, superior fronto-occipital fasciculus, and uncinate fasciculus), and commissural fibers (genu, body, splenium, and bilateral tapetum of corpus callosum). Furthermore, we also found that MoCA scores correlated with DTI values in all supratentorial WM tracts. The results suggested that SIVD patients demonstrated abnormal WM connectivity in all supratentorial regions. Moreover, the severity of damage in WM tracts correlated with cognitive dysfunction.

  8. The contribution of brain sub-cortical loops in the expression and acquisition of action understanding abilities☆

    PubMed Central

    Caligiore, Daniele; Pezzulo, Giovanni; Miall, R. Chris; Baldassarre, Gianluca

    2013-01-01

    Research on action understanding in cognitive neuroscience has led to the identification of a wide “action understanding network” mainly encompassing parietal and premotor cortical areas. Within this cortical network mirror neurons are critically involved implementing a neural mechanism according to which, during action understanding, observed actions are reflected in the motor patterns for the same actions of the observer. We suggest that focusing only on cortical areas and processes could be too restrictive to explain important facets of action understanding regarding, for example, the influence of the observer's motor experience, the multiple levels at which an observed action can be understood, and the acquisition of action understanding ability. In this respect, we propose that aside from the cortical action understanding network, sub-cortical processes pivoting on cerebellar and basal ganglia cortical loops could crucially support both the expression and the acquisition of action understanding abilities. Within the paper we will discuss how this extended view can overcome some limitations of the “pure” cortical perspective, supporting new theoretical predictions on the brain mechanisms underlying action understanding that could be tested by future empirical investigations. PMID:23911926

  9. Biomimetic race model of the loop between the superior colliculus and the basal ganglia: Subcortical selection of saccade targets.

    PubMed

    Thurat, Charles; N'Guyen, Steve; Girard, Benoît

    2015-07-01

    The superior colliculus, a laminar structure involved in the retinotopic mapping of the visual field, plays a cardinal role in several cortical and subcortical pathways of the saccadic system. Although the selection of saccade targets has long been thought to be mainly the product of cortical processes, a growing body of evidence hints at the implication of the superior colliculus in selection processes independent from cortical inputs, capable of producing saccades at latencies incompatible with the cortical pathways. This selection ability could be produced firstly by the lateral connections between the neurons of its maps, and secondly by its interactions with the midbrain basal ganglia, already renowned for their role in decision making. We propose a biomimetic population-coded race model of selection based on a dynamic tecto-basal loop that reproduces the observed ability of the superior colliculus to stochastically select between similar stimuli. Our model's selection accuracy depends on the discriminability of the target and the distractors. Our model also offers an explanation for the phenomenon of Remote Distractor Effect based on the lateral connectivity within the basal ganglia circuitry rather than on lateral inhibitions within the collicular maps. Finally, we propose a role for the intermediate layers of the superior colliculus, as stochastic integrators dynamically gated by the selective disinhibition of the basal ganglia channels that is consistent with the recorded activity profiles of these neurons.

  10. Striatal Dopaminergic Innervation Regulates Subthalamic Beta-Oscillations and Cortical-Subcortical Coupling during Movements: Preliminary Evidence in Subjects with Parkinson’s Disease

    PubMed Central

    Canessa, Andrea; Pozzi, Nicolò G.; Arnulfo, Gabriele; Brumberg, Joachim; Reich, Martin M.; Pezzoli, Gianni; Ghilardi, Maria F.; Matthies, Cordula; Steigerwald, Frank; Volkmann, Jens; Isaias, Ioannis U.

    2016-01-01

    Activation of the basal ganglia has been shown during the preparation and execution of movement. However, the functional interaction of cortical and subcortical brain areas during movement and the relative contribution of dopaminergic striatal innervation remains unclear. We recorded local field potential (LFP) activity from the subthalamic nucleus (STN) and high-density electroencephalography (EEG) signals in four patients with Parkinson’s disease (PD) off dopaminergic medication during a multi-joint motor task performed with their dominant and non-dominant hand. Recordings were performed by means of a fully-implantable deep brain stimulation (DBS) device at 4 months after surgery. Three patients also performed a single-photon computed tomography (SPECT) with [123I]N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane (FP-CIT) to assess striatal dopaminergic innervation. Unilateral movement execution led to event-related desynchronization (ERD) followed by a rebound after movement termination event-related synchronization (ERS) of oscillatory beta activity in the STN and primary sensorimotor cortex of both hemispheres. Dopamine deficiency directly influenced movement-related beta-modulation, with greater beta-suppression in the most dopamine-depleted hemisphere for both ipsi- and contralateral hand movements. Cortical-subcortical, but not interhemispheric subcortical coherencies were modulated by movement and influenced by striatal dopaminergic innervation, being stronger in the most dopamine-depleted hemisphere. The data are consistent with a role of dopamine in shielding subcortical structures from an excessive cortical entrapment and cross-hemispheric coupling, thus allowing fine-tuning of movement. PMID:27999534

  11. Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) as a model of small vessel disease: update on clinical, diagnostic, and management aspects.

    PubMed

    Di Donato, Ilaria; Bianchi, Silvia; De Stefano, Nicola; Dichgans, Martin; Dotti, Maria Teresa; Duering, Marco; Jouvent, Eric; Korczyn, Amos D; Lesnik-Oberstein, Saskia A J; Malandrini, Alessandro; Markus, Hugh S; Pantoni, Leonardo; Penco, Silvana; Rufa, Alessandra; Sinanović, Osman; Stojanov, Dragan; Federico, Antonio

    2017-02-24

    Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common and best known monogenic small vessel disease. Here, we review the clinical, neuroimaging, neuropathological, genetic, and therapeutic aspects based on the most relevant articles published between 1994 and 2016 and on the personal experience of the authors, all directly involved in CADASIL research and care. We conclude with some suggestions that may help in the clinical practice and management of these patients.

  12. Subcortical Differences among Youths with Attention-Deficit/Hyperactivity Disorder Compared to Those with Bipolar Disorder With and Without Attention-Deficit/Hyperactivity Disorder

    PubMed Central

    Michael, Emily S.; Terry, Janine E.; Breeze, Janis L.; Hodge, Steven M.; Tang, Lena; Kennedy, David N.; Moore, Constance M.; Makris, Nikos; Caviness, Verne S.; Frazier, Jean A.

    2009-01-01

    Abstract Introduction A significant number of children with bipolar disorder (BP) have co-morbid attention-deficit/hyperactivity disorder (ADHD). It is unknown if these children have neuroimaging findings unique to their co-morbid presentation, or if their brain findings are similar to children diagnosed with BP alone. Method Fifty three children with Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) BP (23 with ADHD, 30 without), 29 healthy controls (HC), and 23 children with ADHD, similar in sex and age, had magnetic resonance imaging (MRI) scans on a 1.5T GE scanner. Volumetric assessments were performed for basal ganglia and limbic subcortical structures. Results Youths with ADHD had smaller caudate and putamen volumes compared to both BP groups and they had moderately smaller total amygdala volumes compared to the other three groups. Youths with BP + ADHD had moderately larger nucleus accumbens volumes than HC, and females in both BP groups had smaller hippocampal volumes compared to ADHD and HC. No differences were found between the BP and BP + ADHD groups. Conclusion These data suggest that morphometric subcortical volumes in youths with BP + ADHD are more similar to those in youths with BP. They do not share subcortical neuroanatomic correlates with the ADHD group. These findings suggest that BP + ADHD is a subtype of pediatric BP rather than severe ADHD. PMID:19232021

  13. Maturation of Cortico-Subcortical Structural Networks-Segregation and Overlap of Medial Temporal and Fronto-Striatal Systems in Development.

    PubMed

    Walhovd, Kristine B; Tamnes, Christian K; Bjørnerud, Atle; Due-Tønnessen, Paulina; Holland, Dominic; Dale, Anders M; Fjell, Anders M

    2015-07-01

    The brain consists of partly segregated neural circuits within which structural convergence and functional integration occurs during development. The relationship of structural cortical and subcortical maturation is largely unknown. We aimed to study volumetric development of the hippocampus and basal ganglia (caudate, putamen, pallidum, accumbens) in relation to volume changes throughout the cortex. Longitudinal MRI data were obtained across a mean interval of 2.6 years in 85 participants with an age range of 8-19 years at study start. Left and right subcortical changes were related to cortical change vertex-wise in the ipsilateral hemisphere with general linear models with age, sex, interval between scans, and mean cortical volume change as covariates. Hippocampal-cortical change relationships centered on parts of the Papez circuit, including entorhinal, parahippocampal, and isthmus cingulate areas, and lateral temporal, insular, and orbitofrontal cortices in the left hemisphere. Basal ganglia-cortical change relationships were observed in mostly nonoverlapping and more anterior cortical areas, all including the anterior cingulate. Other patterns were unique to specific basal ganglia structures, including pre-, post-, and paracentral patterns relating to putamen change. In conclusion, patterns of cortico-subcortical development as assessed by morphometric analyses in part map out segregated neural circuits at the macrostructural level.

  14. Aggrecan-based extracellular matrix shows unique cortical features and conserved subcortical principles of mammalian brain organization in the Madagascan lesser hedgehog tenrec (Echinops telfairi Martin, 1838).

    PubMed

    Morawski, M; Brückner, G; Jäger, C; Seeger, G; Künzle, H; Arendt, T

    2010-02-03

    The Madagascan tenrecs (Afrotheria), an ancient mammalian clade, are characterized by unique brain anatomy. Striking features are an expanded paleocortex but a small and poorly differentiated neocortex devoid of a distinct granular layer IV. To investigate the organization of cortical areas we analyzed extracellular matrix components in perineuronal nets (PNs) using antibodies to aggrecan, lectin staining and hyaluronan-binding protein. Selected subcortical regions were studied to correlate the cortical patterns with features in evolutionary conserved systems. In the neocortex, paleocortex and hippocampus PNs were associated with nonpyramidal neurons. Quantitative analysis in the cerebral cortex revealed area-specific proportions and laminar distribution patterns of neurons ensheathed by PNs. Cortical PNs showed divergent structural phenotypes. Diffuse PNs forming a cotton wool-like perisomatic rim were characteristic of the paleocortex. These PNs were associated with a dense pericellular plexus of calretinin-immunoreactive fibres. Clearly contoured PNs were devoid of a calretinin-positive plexus and predominated in the neocortex and hippocampus. The organization of the extracellular matrix in subcortical nuclei followed the widely distributed mammalian type. We conclude that molecular properties of the aggrecan-based extracellular matrix are conserved during evolution of mammals; however, the matrix scaffold is adapted to specific wiring patterns of cortical and subcortical neuronal networks.

  15. Altered structural and functional connectivity between the bilateral primary motor cortex in unilateral subcortical stroke: A multimodal magnetic resonance imaging study.

    PubMed

    Zhang, Yong; Li, Kuang-Shi; Ning, Yan-Zhe; Fu, Cai-Hong; Liu, Hong-Wei; Han, Xiao; Cui, Fang-Yuan; Ren, Yi; Zou, Yi-Huai

    2016-08-01

    A large number of functional imaging studies have focused on the understanding of motor-related neural activities after ischemic stroke. However, the knowledge is still limited in the structural and functional changes of the interhemispheric connections of the bilateral primary motor cortices (M1s) and their potential influence on motor function recovery following stroke.Twenty-four stroke patients with right hemispheric subcortical infarcts and 25 control subjects were recruited to undergo multimodal magnetic resonance imaging examinations. Structural impairments between the bilateral M1s were measured by fractional anisotropy. Functional changes of the bilateral M1s were assessed via M1-M1 resting-state functional connectivity. Task-evoked activation analysis was applied to identify the roles of the bilateral hemispheres in motor function recovery. Compared with control subjects, unilateral subcortical stroke patients revealed significantly decreased fractional anisotropy and functional connectivity between the bilateral M1s. Stroke patients also revealed higher activations in multiple brain regions in both hemispheres and that more regions were located in the contralesional hemisphere.This study increased our understanding of the structural and functional alterations between the bilateral M1s that occur in unilateral subcortical stroke and provided further evidence for the compensatory role played by the contralesional hemisphere for these alterations during motor function recovery.

  16. Neonatal Hyperoxia Exposure Disrupts Axon-Oligodendrocyte Integrity in the Sub-Cortical White Matter

    PubMed Central

    Ritter, Jonathan; Schmitz, Thomas; Chew, Li-Jin; Bührer, Christoph; Möbius, Wiebke; Zonouzi, Marzieh; Gallo, Vittorio

    2013-01-01

    The pathological mechanisms underlying neurological deficits observed in individuals born pre-maturely are not completely understood. A common form of injury in the pre-term population is periventricular white matter injury (PWMI), a pathology associated with impaired brain development. To mitigate or eliminate white matter injury, there is an urgent need to understand the pathological mechanism(s) involved on a neurobiological, structural and functional level. Recent clinical data suggests that a percentage of pre-mature infants experience relative hyperoxia. Using a hyperoxic model of pre-mature brain injury, we have previously demonstrated that neonatal hyperoxia exposure in the mouse disrupts development of the white matter (WM) by delaying the maturation of the oligodendroglial lineage. In the present study, we address the question of how hyperoxia-induced alterations in WM development affect overall WM integrity and axonal function. We show that neonatal hyperoxia causes ultra-structural changes, including i) myelination abnormalities (reduced myelin thickness and abnormal extra myelin loops) and ii) axonopathy (altered neurofilament phosphorylation, paranodal defects and changes in node of Ranvier number and structure). This disruption of axon-oligodendrocyte integrity results in the lasting impairment of conduction properties in the adult WM. Understanding the pathology of pre-mature PWMI injury will allow for the development of interventional strategies to preserve WM integrity and function. PMID:23699510

  17. Frequency-selective control of cortical and subcortical networks by central thalamus

    PubMed Central

    Liu, Jia; Lee, Hyun Joo; Weitz, Andrew J; Fang, Zhongnan; Lin, Peter; Choy, ManKin; Fisher, Robert; Pinskiy, Vadim; Tolpygo, Alexander; Mitra, Partha; Schiff, Nicholas; Lee, Jin Hyung

    2015-01-01

    Central thalamus plays a critical role in forebrain arousal and organized behavior. However, network-level mechanisms that link its activity to brain state remain enigmatic. Here, we combined optogenetics, fMRI, electrophysiology, and video-EEG monitoring to characterize the central thalamus-driven global brain networks responsible for switching brain state. 40 and 100 Hz stimulations of central thalamus caused widespread activation of forebrain, including frontal cortex, sensorimotor cortex, and striatum, and transitioned the brain to a state of arousal in asleep rats. In contrast, 10 Hz stimulation evoked significantly less activation of forebrain, inhibition of sensory cortex, and behavioral arrest. To investigate possible mechanisms underlying the frequency-dependent cortical inhibition, we performed recordings in zona incerta, where 10, but not 40, Hz stimulation evoked spindle-like oscillations. Importantly, suppressing incertal activity during 10 Hz central thalamus stimulation reduced the evoked cortical inhibition. These findings identify key brain-wide dynamics underlying central thalamus arousal regulation. DOI: http://dx.doi.org/10.7554/eLife.09215.001 PMID:26652162

  18. Rapid Changes in Cortical and Subcortical Brain Regions after Early Bilateral Enucleation in the Mouse

    PubMed Central

    Huffman, Kelly J.

    2015-01-01

    Functional sensory and motor areas in the developing mammalian neocortex are formed through a complex interaction of cortically intrinsic mechanisms, such as gene expression, and cortically extrinsic mechanisms such as those mediated by thalamic input from the senses. Both intrinsic and extrinsic mechanisms are believed to be involved in cortical patterning and the establishment of areal boundaries in early development; however, the nature of the interaction between intrinsic and extrinsic processes is not well understood. In a previous study, we used a perinatal bilateral enucleation mouse model to test some aspects of this interaction by reweighting sensory input to the developing cortex. Visual deprivation at birth resulted in a shift of intraneocortical connections (INCs) that aligned with ectopic ephrin A5 expression in the same location ten days later at postnatal day (P) 10. A prevailing question remained: Does visual deprivation first induce a change in gene expression, followed by a shift in INCs, or vice versa? In the present study, we address this question by investigating the neuroanatomy and patterns of gene expression in post-natal day (P) 1 and 4 mice following bilateral enucleation at birth. Our results demonstrate a rapid reduction in dorsal lateral geniculate nucleus (dLGN) size and ephrin A5 gene expression 24-hours post-enucleation, with more profound effects apparent at P4. The reduced nuclear size and diminished gene expression mirrors subtle changes in ephrin A5 expression evident in P1 and P4 enucleated neocortex, 11 and 8 days prior to natural eye opening, respectively. Somatosensory and visual INCs were indistinguishable between P1 and P4 mice bilaterally enucleated at birth, indicating that perinatal bilateral enucleation initiates a rapid change in gene expression (within one day) followed by an alteration of sensory INCs later on (second postnatal week). With these results, we gain a deeper understanding of how gene expression and

  19. Causal connectivity alterations of cortical-subcortical circuit anchored on reduced hemodynamic response brain regions in first-episode drug-naïve major depressive disorder

    PubMed Central

    Gao, Qing; Zou, Ke; He, Zongling; Sun, Xueli; Chen, Huafu

    2016-01-01

    Some efforts were done to investigate the disruption of brain causal connectivity networks involved in major depressive disorder (MDD) using Granger causality (GC) analysis. However, the homogenous hemodynamic response function (HRF) assumption over the brain may disturb the inference of temporal precedence. Here we applied a blind deconvolution approach to examine the altered HRF shape in first-episode, drug-naïve MDD patients. The regions with abnormal HRF shape in patients were chosen as seeds to detect the GC alterations in MDD. The results demonstrated significantly decreased magnitude of spontaneous hemodynamic response of the orbital frontal cortex (OFC) and the caudate nucleus (CAU) in MDD comparing to healthy controls, suggesting MDD patients likely had alterations in neurovascular coupling and cerebrovascular physiology in these two regions. GC mapping showed increased/decreased GC in OFC-/CAU centered networks in MDD. The outgoing GC values from OFC to anterior cingulate cortex and occipital regions were positively correlated with Hamilton Depression Scale (HAMD) scores, while the incoming GC from insula, middle and superior temporal gyrus to CAU were negatively correlated with HAMD scores of MDD. The abnormalities of directional connections in the cortico-subcortico-cerebellar network may lead to unbalanced integrating the emotional-related information for MDD, and further exacerbating depressive symptoms. PMID:26911651

  20. Brain mediators of cardiovascular responses to social threat, Part II: Prefrontal-subcortical pathways and relationship with anxiety

    PubMed Central

    Wager, Tor D.; van Ast, Vanessa A.; Hughes, Brent L.; Davidson, Matthew L.; Lindquist, Martin A.; Ochsner, Kevin N.

    2009-01-01

    Social evaluative threat (SET) is a potent stressor in humans linked to autonomic and endocrine responses, and multiple health problems. Neuroimaging has recently begun to elucidate the brain correlates of SET, but as yet little is known about the mediating cortical-brainstem pathways in humans. This paper replicates and extends findings in a companion paper (Wager et al., submitted) using an independent cohort of participants and different image acquisition parameters. Here, we focused specifically on relationships between the medial prefrontal cortex (MPFC), midbrain periaqueductal gray (PAG), and heart rate (HR). We applied multi-level path analysis to localize brain mediators of SET effects on HR and self-reported anxiety. HR responses were mediated by opposing signals in two distinct sub-regions of the MPFC—increases in rostral dorsal anterior cingulate cortex (rdACC) and deactivation in ventromedial prefrontal cortex (vmPFC). In addition, HR responses were mediated by PAG. Additional path analyses provided support for two cortical subcortical pathways: one linking vmPFC, PAG, and HR, and another linking rdACC, thalamus, and HR. PAG responses were linked with HR changes both before and during SET, whereas cortical regions showed stronger connectivity with HR during threat. Self-reported anxiety showed a partially overlapping, but weaker, pattern of mediators, including the vmPFC, dorsomedial PFC (dmPFC), and lateral frontal cortex, as well as substantial individual differences that were largely unexplained. Taken together, these data suggest pathways for the translation of social threats into both physiological and experiential responses, and provide targets for future research on the generation and regulation of emotion. PMID:19465135

  1. Baseline shape diffeomorphometry patterns of subcortical and ventricular structures in predicting conversion of mild cognitive impairment to Alzheimer's disease.

    PubMed

    Tang, Xiaoying; Holland, Dominic; Dale, Anders M; Younes, Laurent; Miller, Michael I

    2015-01-01

    In this paper, we propose a novel predictor for the conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD). This predictor is based on the shape diffeomorphometry patterns of subcortical and ventricular structures (left and right amygdala, hippocampus, thalamus, caudate, putamen, globus pallidus, and lateral ventricle) of 607 baseline scans from the Alzheimer's Disease Neuroimaging Initiative database, including a total of 210 healthy control subjects, 222 MCI subjects, and 175 AD subjects. The optimal predictor is obtained via a feature selection procedure applied to all of the 14 sets of shape features via linear discriminant analysis, resulting in a combination of the shape diffeomorphometry patterns of the left hippocampus, the left lateral ventricle, the right thalamus, the right caudate, and the bilateral putamen. Via 10-fold cross-validation, we substantiate our method by successfully differentiating 77.04% (104/135) of the MCI subjects who converted to AD within 36 months and 71.26% (62/87) of the non-converters. To be specific, for the MCI-converters, we are capable of correctly predicting 82.35% (14/17) of subjects converting in 6 months, 77.5% (31/40) of subjects converting in 12 months, 74.07% (20/27) of subjects converting in 18 months, 78.13% (25/32) of subjects converting in 24 months, and 73.68% (14/19) of subject converting in 36 months. Statistically significant correlation maps were observed between the shape diffeomorphometry features of each of the 14 structures, especially the bilateral amygdala, hippocampus, lateral ventricle, and two neuropsychological test scores--the Alzheimer's Disease Assessment Scale-Cognitive Behavior Section and the Mini-Mental State Examination.

  2. Similar cortical but not subcortical gray matter abnormalities in women with posttraumatic stress disorder with versus without dissociative identity disorder.

    PubMed

    Chalavi, Sima; Vissia, Eline M; Giesen, Mechteld E; Nijenhuis, Ellert R S; Draijer, Nel; Barker, Gareth J; Veltman, Dick J; Reinders, Antje A T S

    2015-03-30

    Neuroanatomical evidence on the relationship between posttraumatic stress disorder (PTSD) and dissociative disorders is still lacking. We acquired brain structural magnetic resonance imaging (MRI) scans from 17 patients with dissociative identity disorder (DID) and co-morbid PTSD (DID-PTSD) and 16 patients with PTSD but without DID (PTSD-only), and 32 healthy controls (HC), and compared their whole-brain cortical and subcortical gray matter (GM) morphological measurements. Associations between GM measurements and severity of dissociative and depersonalization/derealization symptoms or lifetime traumatizing events were evaluated in the patient groups. DID-PTSD and PTSD-only patients, compared with HC, had similarly smaller cortical GM volumes of the whole brain and of frontal, temporal and insular cortices. DID-PTSD patients additionally showed smaller hippocampal and larger pallidum volumes relative to HC, and larger putamen and pallidum volumes relative to PTSD-only. Severity of lifetime traumatizing events and volume of the hippocampus were negatively correlated. Severity of dissociative and depersonalization/derealization symptoms correlated positively with volume of the putamen and pallidum, and negatively with volume of the inferior parietal cortex. Shared abnormal brain structures in DID-PTSD and PTSD-only, small hippocampal volume in DID-PTSD, more severe lifetime traumatizing events in DID-PTSD compared with PTSD-only, and negative correlations between lifetime traumatizing events and hippocampal volume suggest a trauma-related etiology for DID. Our results provide neurobiological evidence for the side-by-side nosological classification of PTSD and DID in the DSM-5.

  3. Cannabis-related working memory deficits and associated subcortical morphological differences in healthy individuals and schizophrenia subjects.

    PubMed

    Smith, Matthew J; Cobia, Derin J; Wang, Lei; Alpert, Kathryn I; Cronenwett, Will J; Goldman, Morris B; Mamah, Daniel; Barch, Deanna M; Breiter, Hans C; Csernansky, John G

    2014-03-01

    Cannabis use is associated with working memory (WM) impairments; however, the relationship between cannabis use and WM neural circuitry is unclear. We examined whether a cannabis use disorder (CUD) was associated with differences in brain morphology between control subjects with and without a CUD and between schizophrenia subjects with and without a CUD, and whether these differences related to WM and CUD history. Subjects group-matched on demographics included 44 healthy controls, 10 subjects with a CUD history, 28 schizophrenia subjects with no history of substance use disorders, and 15 schizophrenia subjects with a CUD history. Large-deformation high-dimensional brain mapping with magnetic resonance imaging was used to obtain surface-based representations of the striatum, globus pallidus, and thalamus, compared across groups, and correlated with WM and CUD history. Surface maps were generated to visualize morphological differences. There were significant cannabis-related parametric decreases in WM across groups. Similar cannabis-related shape differences were observed in the striatum, globus pallidus, and thalamus in controls and schizophrenia subjects. Cannabis-related striatal and thalamic shape differences correlated with poorer WM and younger age of CUD onset in both groups. Schizophrenia subjects demonstrated cannabis-related neuroanatomical differences that were consistent and exaggerated compared with cannabis-related differences found in controls. The cross-sectional results suggest that both CUD groups were characterized by WM deficits and subcortical neuroanatomical differences. Future longitudinal studies could help determine whether cannabis use contributes to these observed shape differences or whether they are biomarkers of a vulnerability to the effects of cannabis that predate its misuse.

  4. Subcortical band heterotopia in rare affected males can be caused by missense mutations in DCX (XLIS) or LIS1.

    PubMed

    Pilz, D T; Kuc, J; Matsumoto, N; Bodurtha, J; Bernadi, B; Tassinari, C A; Dobyns, W B; Ledbetter, D H

    1999-09-01

    Subcortical band heterotopia (SBH) are bilateral and symmetric ribbons of gray matter found in the central white matter between the cortex and the ventricular surface, which comprises the less severe end of the lissencephaly (agyria-pachygyria-band) spectrum of malformations. Mutations in DCX (also known as XLIS ) have previously been described in females with SBH. We have now identified mutations in either the DCX or LIS1 gene in three of 11 boys studied, demonstrating for the first time that mutations of either DCX or LIS1 can cause SBH or mixed pachygyria-SBH (PCH-SBH) in males. All three changes detected are missense mutations, predicted to be of germline origin. They include a missense mutation in exon 4 of DCX in a boy with PCH-SBH (R78H), a different missense mutation in exon 4 of DCX in a boy with mild SBH and in his mildly affected mother (R89G) and a missense mutation in exon 6 of LIS1 in a boy with SBH (S169P). The missense mutations probably account for the less severe brain malformations, although other patients with missense mutations in the same exons have had diffuse lissencephaly. Therefore, it appears likely that the effect of the specific amino acid change on the protein determines the severity of the phenotype, with some mutations enabling residual protein function and allowing normal migration in a larger proportion of neurons. However, we expect that somatic mosaic mutations of both LIS1 and DCX will also prove to be an important mechanism in causing SBH in males.

  5. Mutant GlialCAM Causes Megalencephalic Leukoencephalopathy with Subcortical Cysts, Benign Familial Macrocephaly, and Macrocephaly with Retardation and Autism

    PubMed Central

    López-Hernández, Tania; Ridder, Margreet C.; Montolio, Marisol; Capdevila-Nortes, Xavier; Polder, Emiel; Sirisi, Sònia; Duarri, Anna; Schulte, Uwe; Fakler, Bernd; Nunes, Virginia; Scheper, Gert C.; Martínez, Albert; Estévez, Raúl; van der Knaap, Marjo S.

    2011-01-01

    Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a leukodystrophy characterized by early-onset macrocephaly and delayed-onset neurological deterioration. Recessive MLC1 mutations are observed in 75% of patients with MLC. Genetic-linkage studies failed to identify another gene. We recently showed that some patients without MLC1 mutations display the classical phenotype; others improve or become normal but retain macrocephaly. To find another MLC-related gene, we used quantitative proteomic analysis of affinity-purified MLC1 as an alternative approach and found that GlialCAM, an IgG-like cell adhesion molecule that is also called HepaCAM and is encoded by HEPACAM, is a direct MLC1-binding partner. Analysis of 40 MLC patients without MLC1 mutations revealed multiple different HEPACAM mutations. Ten patients with the classical, deteriorating phenotype had two mutations, and 18 patients with the improving phenotype had one mutation. Most parents with a single mutation had macrocephaly, indicating dominant inheritance. In some families with dominant HEPACAM mutations, the clinical picture and magnetic resonance imaging normalized, indicating that HEPACAM mutations can cause benign familial macrocephaly. In other families with dominant HEPACAM mutations, patients had macrocephaly and mental retardation with or without autism. Further experiments demonstrated that GlialCAM and MLC1 both localize in axons and colocalize in junctions between astrocytes. GlialCAM is additionally located in myelin. Mutant GlialCAM disrupts the localization of MLC1-GlialCAM complexes in astrocytic junctions in a manner reflecting the mode of inheritance. In conclusion, GlialCAM is required for proper localization of MLC1. HEPACAM is the second gene found to be mutated in MLC. Dominant HEPACAM mutations can cause either macrocephaly and mental retardation with or without autism or benign familial macrocephaly. PMID:21419380

  6. Early-life lead exposure recapitulates the selective loss of parvalbumin-positive GABAergic interneurons and subcortical dopamine system hyperactivity present in schizophrenia.

    PubMed

    Stansfield, K H; Ruby, K N; Soares, B D; McGlothan, J L; Liu, X; Guilarte, T R

    2015-03-10

    Environmental factors have been associated with psychiatric disorders and recent epidemiological studies suggest an association between prenatal lead (Pb(2+)) exposure and schizophrenia (SZ). Pb(2+) is a potent antagonist of the N-methyl-D-aspartate receptor (NMDAR) and converging evidence indicates that NMDAR hypofunction has a key role in the pathophysiology of SZ. The glutamatergic hypothesis of SZ posits that NMDAR hypofunction results in the loss of parvalbumin (PV)-positive GABAergic interneurons (PVGI) in the brain. Loss of PVGI inhibitory control to pyramidal cells alters the excitatory drive to midbrain dopamine neurons increasing subcortical dopaminergic activity. We hypothesized that if Pb(2+) exposure in early life is an environmental risk factor for SZ, it should recapitulate the loss of PVGI and reproduce subcortical dopaminergic hyperactivity. We report that on postnatal day 50 (PN50), adolescence rats chronically exposed to Pb(2+) from gestation through adolescence exhibit loss of PVGI in SZ-relevant brain regions. PV and glutamic acid decarboxylase 67 kDa (GAD67) protein were significantly decreased in Pb(2+) exposed rats with no apparent change in calretinin or calbindin protein levels suggesting a selective effect on the PV phenotype of GABAergic interneurons. We also show that Pb(2+) animals exhibit a heightened locomotor response to cocaine and express significantly higher levels of dopamine metabolites and D2-dopamine receptors relative to controls indicative of subcortical dopaminergic hyperactivity. Our results show that developmental Pb(2+) exposure reproduces specific neuropathology and functional dopamine system changes present in SZ. We propose that exposure to environmental toxins that produce NMDAR hypofunction during critical periods of brain development may contribute significantly to the etiology of mental disorders.

  7. Assessment of Age-Related Morphometric Changes of Subcortical Structures in Healthy People Using Ultra-High Field 7 Tesla Magnetic Resonance Imaging

    PubMed Central

    Wang, Xue-Yuan; Zhao, Lei; Yu, Tao; Qiao, Liang; Ni, Duan-Yu; Zhang, Guo-Jun; Li, Yong-Jie

    2016-01-01

    Objective: To assess the age-related morphometric changes of subcortical structures in healthy people. Materials and Methods: Ultra-high field 7 tesla magnetic resonance (MR) imaging in humans was used to visualize the subcortical structures of healthy young, middle-aged and elderly participants. Using the magnetization-prepared two rapid acquisition gradient echo (MP2RAGE) sequence, we assessed the visibility of the margins of the thalamus and white matter in the thalamus, as well as the anterior commissure (AC) and posterior commissure (PC) length, the maximal height of the thalamus, the half width of the third ventricle and the distance between the AC and the center of the mammillothalamic tract (MTT) at the level of the AC-PC plane. All quantitative data were statistically evaluated. Results: The AC-PC length did not differ significantly among the three groups. The maximal height of the thalamus decreased with age (rs(53) = −0.719, p < 0.001). The half width of the third ventricle (rs(53) = 0.705, p < 0.001) and the distance between the AC and the center of the MTT (rs(53) = 0.485, p < 0.001) increased with age. The distance between the AC and the center of the MTT of the young and the elderly participants differed significantly (p = 0.007). Conclusion: The AC-PC length is not a good candidate for proportional correction during atlas-to-patient registration. The maximal height of the thalamus and the half width of the third ventricle correlated strongly with age, and the MTT position in relation to the AC shifted posteriorly as age increased. These age-related morphometric changes of subcortical structures should be considered in targeting for functional neurosurgery. PMID:27725800

  8. Beyond age and gender: relationships between cortical and subcortical brain volume and cognitive-motor abilities in school-age children.

    PubMed

    Pangelinan, Melissa M; Zhang, Guangyu; VanMeter, John W; Clark, Jane E; Hatfield, Bradley D; Haufler, Amy J

    2011-02-14

    There is growing evidence that cognitive and motor functions are interrelated and may rely on the development of the same cortical and subcortical neural structures. However, no study to date has examined the relationships between brain volume, cognitive ability, and motor ability in typically developing children. The NIH MRI Study of Normal Brain Development consists of a large, longitudinal database of structural MRI and performance measures from a battery of neuropsychological assessments from typically developing children. This dataset provides a unique opportunity to examine relationships between the brain and cognitive-motor abilities. A secondary analysis was conducted on data from 172 children between the ages of 6 to 13 years with up to 2 measurement occasions (initial testing and 2-year follow-up). Linear mixed effects modeling was employed to account for age and gender effects on the development of specific cortical and subcortical volumes as well as behavioral performance measures of interest. Above and beyond the effects of age and gender, significant relationships were found between general cognitive ability (IQ) and the volume of subcortical brain structures (cerebellum and caudate) as well as spatial working memory and the putamen. In addition, IQ was found to be related to global and frontal gray matter volume as well as parietal gray and white matter. At the behavioral level, general cognitive ability was also found to be related to visuomotor ability (pegboard) and executive function (spatial working memory). These results support the notion that cognition and motor skills may be fundamentally interrelated at both the levels of behavior and brain structure.

  9. Beyond age and gender: Relationships between cortical and subcortical brain volume and cognitive-motor abilities in school-age children

    PubMed Central

    Pangelinan, Melissa M.; Zhang, Guangyu; VanMeter, John W.; Clark, Jane E.; Hatfield, Bradley D.; Haufler, Amy J.

    2010-01-01

    There is growing evidence that cognitive and motor functions are interrelated and may rely on the development of the same cortical and subcortical neural structures. However, no study to date has examined the relationships between brain volume, cognitive ability, and motor ability in typically developing children. The NIH MRI Study of Normal Brain Development consists of a large, longitudinal database of structural MRI and performance measures from a battery of neuropsychological assessments from typically developing children. This dataset provides a unique opportunity to examine relationships between the brain and cognitive-motor abilities. A secondary analysis was conducted on data from 172 children between the ages of 6 to 13 years with up to 2 measurement occasions (initial testing and 2-year follow-up). Linear mixed effects modeling was employed to account for age and gender effects on the development of specific cortical and subcortical volumes as well as behavioral performance measures of interest. Above and beyond the effects of age and gender, significant relationships were found between general cognitive ability (IQ) and the volume of subcortical brain structures (cerebellum and caudate) as well as spatial working memory and the putamen. In addition, IQ was found to be related to global and frontal gray matter volume as well as parietal gray and white matter. At the behavioral level, general cognitive ability was also found to be related to visuomotor ability (pegboard) and executive function (spatial working memory). These results support the notion that cognition and motor skills may be fundamentally interrelated at both the levels of behavior and brain structure. PMID:21078402

  10. Desire and Dread from the Nucleus Accumbens: Cortical Glutamate and Subcortical GABA Differentially Generate Motivation and Hedonic Impact in the Rat

    PubMed Central

    Faure, Alexis; Richard, Jocelyn M.; Berridge, Kent C.

    2010-01-01

    Background GABAergic signals to the nucleus accumbens (NAc) shell arise from predominantly subcortical sources whereas glutamatergic signals arise mainly from cortical-related sources. Here we contrasted GABAergic and glutamatergic generation of hedonics versus motivation processes, as a proxy for comparing subcortical and cortical controls of emotion. Local disruptions of either signals in medial shell of NAc generate intense motivated behaviors corresponding to desire and/or dread, along a rostrocaudal gradient. GABA or glutamate disruptions in rostral shell generate appetitive motivation whereas disruptions in caudal shell elicit fearful motivation. However, GABA and glutamate signals in NAc differ in important ways, despite the similarity of their rostrocaudal motivation gradients. Methodology/Principal Findings Microinjections of a GABAA agonist (muscimol), or of a glutamate AMPA antagonist (DNQX) in medial shell of rats were assessed for generation of hedonic “liking” or “disliking” by measuring orofacial affective reactions to sucrose-quinine taste. Motivation generation was independently assessed measuring effects on eating versus natural defensive behaviors. For GABAergic microinjections, we found that the desire-dread motivation gradient was mirrored by an equivalent hedonic gradient that amplified affective taste “liking” (at rostral sites) versus “disliking” (at caudal sites). However, manipulation of glutamatergic signals completely failed to alter pleasure-displeasure reactions to sensory hedonic impact, despite producing a strong rostrocaudal gradient of motivation. Conclusions/Significance We conclude that the nucleus accumbens contains two functional affective keyboards for amino-acid signals: a motivation-generating keyboard and a hedonic-generating keyboard. Corticolimbic glutamate signals and subcortical GABA signals equivalently engage the motivation keyboard to generate desire and-or dread. Only subcortical GABA signals

  11. Cortico-subcortical visual, somatosensory, and motor activations for perceiving dynamic whole-body emotional expressions with and without striate cortex (V1)

    PubMed Central

    Van den Stock, Jan; Tamietto, Marco; Sorger, Bettina; Pichon, Swann; Grézes, Julie; de Gelder, Beatrice

    2011-01-01

    Patients with striate cortex damage and clinical blindness retain the ability to process certain visual properties of stimuli that they are not aware of seeing. Here we investigated the neural correlates of residual visual perception for dynamic whole-body emotional actions. Angry and neutral emotional whole-body actions were presented in the intact and blind visual hemifield of a cortically blind patient with unilateral destruction of striate cortex. Comparisons of angry vs. neutral actions performed separately in the blind and intact visual hemifield showed in both cases increased activation in primary somatosensory, motor, and premotor cortices. Activations selective for intact hemifield presentation of angry compared with neutral actions were located subcortically in the right lateral geniculate nucleus and cortically in the superior temporal sulcus, prefrontal cortex, precuneus, and intraparietal sulcus. Activations specific for blind hemifield presentation of angry compared with neutral actions were found in the bilateral superior colliculus, pulvinar nucleus of the thalamus, amygdala, and right fusiform gyrus. Direct comparison of emotional modulation in the blind vs. intact visual hemifield revealed selective activity in the right superior colliculus and bilateral pulvinar for angry expressions, thereby showing a selective involvement of these subcortical structures in nonconscious visual emotion perception. PMID:21911384

  12. Cognitive patterns of normal elderly subjects are consistent with frontal cortico-subcortical and fronto-parietal neuropsychological models of brain aging.

    PubMed

    Gawron, Natalia; Łojek, Emilia; Kijanowska-Haładyna, Beata; Nestorowicz, Jakub; Harasim, Andrzej; Pluta, Agnieszka; Sobańska, Marta

    2014-01-01

    Three neuropsychological theories have been developed according to a possible existence of a similar pattern of cognitive decline in elderly individuals and patients with brain damage. The respective neuropsychological theories attribute age-related deficits to: (a) dysfunction of the frontal lobes, (b) temporo-parietal dysfunction, or (c) decline of right-hemisphere functions. In the present study, we examined which of these theories best explains the cognitive patterns of normal elderly subjects older than 80 years of age (old elderly). Thirty normal old elderly subjects, 14 patients with subcortical vascular dementia, 14 with mild Alzheimer's disease, 15 with damage of the right hemisphere of the brain, and 20 young elderly controls participated. A test battery covering the main cognitive domains was administered to all participants. A hierarchical cluster analysis revealed five groups of individuals with different cognitive patterns across the whole sample. Old elderly subjects were assigned to four groups according to: (a) preserved overall cognitive performance, (b) processing speed decline, (c) attention decline, or (d) executive impairment. The results of the study are most congruent with models emphasizing frontal-lobe cortical-subcortical and fronto-parietal changes in old age. The results also indicate considerable heterogeneity in the cognitive patterns of normal old elderly adults.

  13. Joint assessment of white matter integrity, cortical and subcortical atrophy to distinguish AD from behavioral variant FTD: A two-center study.

    PubMed

    Möller, Christiane; Hafkemeijer, Anne; Pijnenburg, Yolande A L; Rombouts, Serge A R B; van der Grond, Jeroen; Dopper, Elise; van Swieten, John; Versteeg, Adriaan; Pouwels, Petra J W; Barkhof, Frederik; Scheltens, Philip; Vrenken, Hugo; van der Flier, Wiesje M

    2015-01-01

    We investigated the ability of cortical and subcortical gray matter (GM) atrophy in combination with white matter (WM) integrity to distinguish behavioral variant frontotemporal dementia (bvFTD) from Alzheimer's disease (AD) and from controls using voxel-based morphometry, subcortical structure segmentation, and tract-based spatial statistics. To determine which combination of MR markers differentiated the three groups with the highest accuracy, we conducted discriminant function analyses. Adjusted for age, sex and center, both types of dementia had more GM atrophy, lower fractional anisotropy (FA) and higher mean (MD), axial (L1) and radial diffusivity (L23) values than controls. BvFTD patients had more GM atrophy in orbitofrontal and inferior frontal areas than AD patients. In addition, caudate nucleus and nucleus accumbens were smaller in bvFTD than in AD. FA values were lower; MD, L1 and L23 values were higher, especially in frontal areas of the brain for bvFTD compared to AD patients. The combination of cortical GM, hippocampal volume and WM integrity measurements, classified 97-100% of controls, 81-100% of AD and 67-75% of bvFTD patients correctly. Our results suggest that WM integrity measures add complementary information to measures of GM atrophy, thereby improving the classification between AD and bvFTD.

  14. Reappraising contemporary theories of subcortical participation in language: proposing an interhemispheric regulatory function for the subthalamic nucleus (STN) in the mediation of high-level linguistic processes.

    PubMed

    Whelan, Brooke-Mai; Murdoch, Bruce E; Theodoros, Deborah G; Silburn, Peter; Hall, Bruce

    2004-02-01

    Apropos the basal ganglia, the dominant striatum and globus pallidus internus (GPi) have been hypothesised to represent integral components of subcortical language circuitry. Working subcortical language theories, however, have failed thus far to consider a role for the STN in the mediation of linguistic processes, a structure recently defined as the driving force of basal ganglia output. The aim of this research was to investigate the impact of surgically induced functional inhibition of the STN upon linguistic abilities, within the context of established models of basal ganglia participation in language. Two males with surgically induced 'lesions' of the dominant and non-dominant dorsolateral STN, aimed at relieving Parkinsonian motor symptoms, served as experimental subjects. General and high-level language profiles were compiled for each subject up to 1 month prior to and 3 months following neurosurgery, within the drug-on state (i.e., when optimally medicated). Comparable post-operative alterations in linguistic performance were observed subsequent to surgically induced functional inhibition of the left and right STN. More specifically, higher proportions of reliable decline as opposed to improvement in post-operative performance were demonstrated by both subjects on complex language tasks, hypothesised to entail the interplay of cognitive-linguistic processes. The outcomes of the current research challenge unilateralised models of functional basal ganglia organisation with the proposal of a potential interhemispheric regulatory function for the STN in the mediation of high-level linguistic processes.

  15. Detection of cerebral amyloid angiopathy by 3-T magnetic resonance imaging and amyloid positron emission tomography in a patient with subcortical ischaemic vascular dementia.

    PubMed

    Kida, Hirotaka; Satoh, Masayuki; Ii, Yuichiro; Fukuyama, Hidenao; Maeda, Masayuki; Tomimoto, Hidekazu

    2017-01-01

    The patient was an 81-year-old man who had been treated for hypertension for several decades. In 2012, he developed gait disturbance and mild amnesia. One year later, his gait disturbance worsened, and he developed urinary incontinence. Conventional brain magnetic resonance imaging using T 2 -weighted images and fluid-attenuated inversion recovery showed multiple lacunar infarctions. These findings fulfilled the diagnostic criteria for subcortical ischaemic vascular dementia. However, susceptibility weighted imaging showed multiple lobar microbleeds in the bilateral occipitoparietal lobes, and double inversion recovery and 3-D fluid-attenuated inversion recovery images on 3-T magnetic resonance imaging revealed cortical microinfarctions in the left parietal-temporo-occipito region. Pittsburgh compound B-positron emission tomography revealed diffuse uptake in the cerebral cortex. Therefore, we diagnosed the patient with subcortical ischaemic vascular dementia associated with Alzheimer's disease. The use of the double inversion recovery and susceptibility weighted imaging on 3-T magnetic resonance imaging may be a supplemental strategy for diagnosing cerebral amyloid angiopathy, which is closely associated with Alzheimer's disease.

  16. Joint assessment of white matter integrity, cortical and subcortical atrophy to distinguish AD from behavioral variant FTD: A two-center study

    PubMed Central

    Möller, Christiane; Hafkemeijer, Anne; Pijnenburg, Yolande A.L.; Rombouts, Serge A.R.B.; van der Grond, Jeroen; Dopper, Elise; van Swieten, John; Versteeg, Adriaan; Pouwels, Petra J.W.; Barkhof, Frederik; Scheltens, Philip; Vrenken, Hugo; van der Flier, Wiesje M.

    2015-01-01

    We investigated the ability of cortical and subcortical gray matter (GM) atrophy in combination with white matter (WM) integrity to distinguish behavioral variant frontotemporal dementia (bvFTD) from Alzheimer's disease (AD) and from controls using voxel-based morphometry, subcortical structure segmentation, and tract-based spatial statistics. To determine which combination of MR markers differentiated the three groups with the highest accuracy, we conducted discriminant function analyses. Adjusted for age, sex and center, both types of dementia had more GM atrophy, lower fractional anisotropy (FA) and higher mean (MD), axial (L1) and radial diffusivity (L23) values than controls. BvFTD patients had more GM atrophy in orbitofrontal and inferior frontal areas than AD patients. In addition, caudate nucleus and nucleus accumbens were smaller in bvFTD than in AD. FA values were lower; MD, L1 and L23 values were higher, especially in frontal areas of the brain for bvFTD compared to AD patients. The combination of cortical GM, hippocampal volume and WM integrity measurements, classified 97–100% of controls, 81–100% of AD and 67–75% of bvFTD patients correctly. Our results suggest that WM integrity measures add complementary information to measures of GM atrophy, thereby improving the classification between AD and bvFTD. PMID:26594624

  17. Cortical Grey Matter and Subcortical White Matter Brain Microstructural Changes in Schizophrenia Are Localised and Age Independent: A Case-Control Diffusion Tensor Imaging Study

    PubMed Central

    Chiapponi, Chiara; Piras, Fabrizio; Piras, Federica; Fagioli, Sabrina; Caltagirone, Carlo; Spalletta, Gianfranco

    2013-01-01

    It is still unknown whether the structural brain impairments that characterize schizophrenia (SZ) worsen during the lifetime. Here, we aimed to describe age-related microstructural brain changes in cortical grey matter and subcortical white matter of patients affected by SZ. In this diffusion tensor imaging study, we included 69 patients diagnosed with SZ and 69 healthy control (HC) subjects, age and gender matched. We carried out analyses of covariance, with diagnosis as fixed factor and brain diffusion-related parameters as dependent variables, and controlled for the effect of education. White matter fractional anisotropy decreased in the entire age range spanned (18–65 years) in both SZ and HC and was significantly lower in younger patients with SZ, with no interaction (age by diagnosis) effect in fiber tracts including corpus callosum, corona radiata, thalamic radiations and external capsule. Also, grey matter mean diffusivity increased in the entire age range in both SZ and HC and was significantly higher in younger patients, with no age by diagnosis interaction in the left frontal operculum cortex, left insula and left planum polare and in the right temporal pole and right intracalcarine cortex. In individuals with SZ we found that localized brain cortical and white matter subcortical microstructural impairments appear early in life but do not worsen in the 18–65 year age range. PMID:24124469

  18. Cortical grey matter and subcortical white matter brain microstructural changes in schizophrenia are localised and age independent: a case-control diffusion tensor imaging study.

    PubMed

    Chiapponi, Chiara; Piras, Fabrizio; Piras, Federica; Fagioli, Sabrina; Caltagirone, Carlo; Spalletta, Gianfranco

    2013-01-01

    It is still unknown whether the structural brain impairments that characterize schizophrenia (SZ) worsen during the lifetime. Here, we aimed to describe age-related microstructural brain changes in cortical grey matter and subcortical white matter of patients affected by SZ. In this diffusion tensor imaging study, we included 69 patients diagnosed with SZ and 69 healthy control (HC) subjects, age and gender matched. We carried out analyses of covariance, with diagnosis as fixed factor and brain diffusion-related parameters as dependent variables, and controlled for the effect of education. White matter fractional anisotropy decreased in the entire age range spanned (18-65 years) in both SZ and HC and was significantly lower in younger patients with SZ, with no interaction (age by diagnosis) effect in fiber tracts including corpus callosum, corona radiata, thalamic radiations and external capsule. Also, grey matter mean diffusivity increased in the entire age range in both SZ and HC and was significantly higher in younger patients, with no age by diagnosis interaction in the left frontal operculum cortex, left insula and left planum polare and in the right temporal pole and right intracalcarine cortex. In individuals with SZ we found that localized brain cortical and white matter subcortical microstructural impairments appear early in life but do not worsen in the 18-65 year age range.

  19. Association of 5' end neuregulin-1 (NRG1) gene variation with subcortical medial frontal microstructure in humans.

    PubMed

    Winterer, Georg; Konrad, Andreas; Vucurevic, Goran; Musso, Francesco; Stoeter, Peter; Dahmen, Norbert

    2008-04-01

    Animal data suggest that the gene neuregulin-1 (NRG1) is involved in neuronal myelination. A haplotype (deCODE) in the 5' end region of the gene was described to double the risk for schizophrenia in an Icelandic population (Stefansson, H., Sigurdsson, E., Steinthorsdottir, V., Bjornsdottir, S., Sigmundsson, T., Ghosh, S., Brynjolfsson, J., Gunnarsdottir, S., Ivarsson, O., Chou, T.T., Hjaltason, O., Birgisdottir, B., Jonsson, H., Gudnadottir, V.G., Gudmundsdottir, E., Bjornsson, A., Ingvarsson, B., Ingason, A., Sigfusson, S., Hardardottir, H., Harvey, R.P., Lai, D., Zhou, M., Brunner, D., Mutel, V., Gonzalo, A., Lemke, G., Sainz, J., Johannesson, G., Andresson, T., Gudbjartsson, D., Manolescu, A., Frigge, M.L., Gurney, M.E., Kong, A., Gulcher, J.R., Petursson, H., Stefansson, K. 2002. Neuregulin-1 and susceptibility to schizophrenia. Am. J. Hum. Genet. 71, 877-892). Of note, there is now increasing evidence of disturbed myelination in this illness--particularly in subcortical frontal lobe white matter (Konrad, A., Winterer, G. 2008. Disturbed structural connectivity in schizophrenia--primary factor in pathology or epiphenomenon? Schiz. Bull. [Electronic publication ahead of print]). Therefore, we investigated with diffusion tensor imaging (DTI) the impact of a tagging single nucleotide polymorphism (SNP) from the deCODE haplotype, i.e., SNP8NRG221533, on fractional anisotropy (FA), which reflects structural integrity of white matter. SNP8NRG221533 was selected because it gave the single best uncorrected association with schizophrenia in the original report by Stefansson et al. (Stefansson, H., Sigurdsson, E., Steinthorsdottir, V., Bjornsdottir, S., Sigmundsson, T., Ghosh, S., Brynjolfsson, J., Gunnarsdottir, S., Ivarsson, O., Chou, T.T., Hjaltason, O., Birgisdottir, B., Jonsson, H., Gudnadottir, V.G., Gudmundsdottir, E., Bjornsson, A., Ingvarsson, B., Ingason, A., Sigfusson, S., Hardardottir, H., Harvey, R.P., Lai, D., Zhou, M., Brunner, D., Mutel, V., Gonzalo, A

  20. Clinical variability of the cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy phenotype in two siblings of a large family showing the same mutation

    PubMed Central

    Vyshka, Gentian; Kruja, Jera

    2013-01-01

    A 44-year-old Albanian male was consulted and diagnosed with dementia. His magnetic resonance imaging suggested diffuse white matter changes. The suspicion of cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) was raised, and a genetic analysis confirmed such a suspicion through uncovering a pathogenic mutation at the level of exon 4 (c.475C>T) of chromosome 19. The patient came from a large family of 13 children, all of whom underwent clinical, genetic, and imaging examination. The pathogenic mutation was found present only in his eldest sister (50 years old), and she presented also very suggestive signs of CADASIL in her respective imaging study, but without any clinically significant counterpart. All other siblings were free from clinical and radiological signs of the disorder. Our opinion was that we were dealing with a mutation showing a very low level of penetrance, with only two siblings affected in a large Albanian family with 13 children. PMID:24124395

  1. Clinical Features and Racial/Ethnic Differences among the 3020 Participants in the Secondary Prevention of Small Subcortical Strokes (SPS3) Trial

    PubMed Central

    White, Carole L.; Szychowski, Jeff M.; Roldan, Ana; Benavente, Marie-France; Pretell, Edwin J.; Del Brutto, Oscar H.; Kase, Carlos S.; Arauz, Antonio; Meyer, Brett C.; Meissner, Irene; Demaerschalk, Bart M.; McClure, Leslie A.; Coffey, Christopher S.; Pearce, Lesly A.; Conwit, Robin; Irby, Lisa H.; Peri, Kalyani; Pergola, Pablo E.; Hart, Robert G.; Benavente, Oscar R.

    2012-01-01

    AIM To describe the baseline characteristics, racial/ethnic differences, and geographic differences among participants in the Secondary Prevention of Small Subcortical Strokes (SPS3) study. METHODS The SPS3 trial enrolled patients with a symptomatic small subcortical stroke (lacunar stroke) within the prior 6 months and an eligible lesion on MRI, who were randomized, in a factorial design, to antiplatelet therapy (aspirin 325 mg daily plus clopidogrel 75 mg daily vs. aspirin 325 mg daily plus placebo) and to one of two levels of systolic blood pressure targets (“intensive” (<130 mmHg) vs. “usual” (130–149 mmHg)). RESULTS Among the 3020 participants recruited from 81 clinical sites in 8 countries, the mean age was 63 years, 63% were men, 75% had a history of hypertension, and 37% were diabetic. Fifty-one percent were White, 30% Hispanic, and 16% Black. Black participants were younger (mean age 58 years vs. 64 years, p<0.001) and more often had hypertension (95% vs. 89%, p<0.001) than White participants. Hispanic and Black participants more often had diabetes than White participants (42%, 40% vs. 32% respectively, both p<0.001). Tobacco smoking at the time of qualifying stroke was much more frequent among Spanish participants (32%) than those from North America (22%) or Latin America (8%) (p<0.001); systolic blood pressure at study entry was 5 mmHg lower among Spanish vs. North American participants (p<0.01). CONCLUSIONS The SPS3 cohort is the largest MRI-defined series of patients with S3. Among the racially/ethnically diverse SPS3 participants, there are important differences in patient features and vascular risk factors could influence prognosis for recurrent stroke and response to interventions. Clinical Trial Registration Information The SPS3 study is registered on www.clinicaltrials.gov (NCT00059306). PMID:22516427

  2. A short-term scan-rescan reliability test measuring brain tissue and subcortical hyperintensity volumetrics obtained using the lesion explorer structural MRI processing pipeline.

    PubMed

    Ramirez, Joel; Scott, Christopher J M; Black, Sandra E

    2013-01-01

    Lesion Explorer (LE) is a reliable and comprehensive MRI-derived tissue segmentation and brain region parcellation processing pipeline for obtaining intracranial tissue and subcortical hyperintensity (SH) volumetrics. The processing pipeline segments: gray (GM) and white matter (WM); sulcal (sCSF) and ventricular cerebrospinal fluid (vCSF); periventricular (pvSH) and deep white subcortical hyperintensities (dwSH); and cystic fluid filled lacunar-like infarcts (Lacunar); into 26 regions of interest. A short-term scan-rescan reliability test was performed on 20 healthy volunteers: 10 older (mean = 77.7 years, SD = 11.1) and 10 younger (mean = 29.4 years, SD = 7.1). Each participant was scanned twice with an average interscan interval of 15.4 days (range: 29 min-50 days). Results suggest low technique-related error as indicated by excellent intraclass correlation coefficient (ICC) results, with ICCs above 0.90 (p < 0.05) for GM, WM, and CSF, in all 26 regions of interest (13 per hemisphere). Ventricular and lesion sub-type (pvSH, dwSH, and Lacunar) volumes also showed high scan-rescan reliability (dwSH = 0.9998, pvSH = 0.9998, Lacunar = 0.9859, p < 0.01). As indicated by the results of this short-term scan-rescan study, the LE structural MRI processing pipeline can be applied for longitudinal volumetric analyses with confidence.

  3. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, genetic homogeneity, and mapping of the locus within a 2-cM interval

    SciTech Connect

    Ducros, A.; Alamowitch, S.; Nagy, T.

    1996-01-01

    Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a recently identified autosomal dominant cerebral arteriopathy characterized by the recurrence of subcortical infarcts leading to dementia. A genetic linkage analysis conducted in two large families recently allowed us to map the affected gene on chromosome 19 in a 12-cM interval bracketed by D19S221 and D19S215. In the present study, these first 2 families and 13 additional ones, including a total of 199 potentially informative meiosis, have been genotyped with eight polymorphic markers located between D19S221 and D19S215. All families were linked to chromosome 19. The highest combined lod score (Z{sub max} = 37.24 at {theta} = .01) was obtained with marker D19S841, a new CA{sub n} microsatellite marker that we isolated from chromosome 19 cosmids. The recombinant events observed within these families were used to refine the genetic mapping of CADASIL within a 2-cM interval that is now bracketed by D19S226 and D19S199 on 19p13.1. These data strongly suggest the genetic homogeneity of this recently identified condition and establish the value of its clinical and neuroimaging diagnostic criteria. Besides their importance for the ongoing positional cloning of the CADASIL gene, these data help to refine the genetic mapping of CADASIL relative to familial hemiplegic migraine and hereditary paroxysmal cerebellar ataxia, conditions that we both mapped within the same chromosome 19 region. 35 refs., 5 figs., 2 tabs.

  4. Nonlinear Y-Like Receptive Fields in the Early Visual Cortex: An Intermediate Stage for Building Cue-Invariant Receptive Fields from Subcortical Y Cells.

    PubMed

    Gharat, Amol; Baker, Curtis L

    2017-01-25

    Many of the neurons in early visual cortex are selective for the orientation of boundaries defined by first-order cues (luminance) as well as second-order cues (contrast, texture). The neural circuit mechanism underlying this selectivity is still unclear, but some studies have proposed that it emerges from spatial nonlinearities of subcortical Y cells. To understand how inputs from the Y-cell pathway might be pooled to generate cue-invariant receptive fields, we recorded visual responses from single neurons in cat Area 18 using linear multielectrode arrays. We measured responses to drifting and contrast-reversing luminance gratings as well as contrast modulation gratings. We found that a large fraction of these neurons have nonoriented responses to gratings, similar to those of subcortical Y cells: they respond at the second harmonic (F2) to high-spatial frequency contrast-reversing gratings and at the first harmonic (F1) to low-spatial frequency drifting gratings ("Y-cell signature"). For a given neuron, spatial frequency tuning for linear (F1) and nonlinear (F2) responses is quite distinct, similar to orientation-selective cue-invariant neurons. Also, these neurons respond to contrast modulation gratings with selectivity for the carrier (texture) spatial frequency and, in some cases, orientation. Their receptive field properties suggest that they could serve as building blocks for orientation-selective cue-invariant neurons. We propose a circuit model that combines ON- and OFF-center cortical Y-like cells in an unbalanced push-pull manner to generate orientation-selective, cue-invariant receptive fields.

  5. Cerebral Blood Flow Alterations as Assessed by 3D ASL in Cognitive Impairment in Patients with Subcortical Vascular Cognitive Impairment: A Marker for Disease Severity

    PubMed Central

    Sun, Yawen; Cao, Wenwei; Ding, Weina; Wang, Yao; Han, Xu; Zhou, Yan; Xu, Qun; Zhang, Yong; Xu, Jianrong

    2016-01-01

    Abnormal reductions in cortical cerebral blood flow (CBF) have been identified in subcortical vascular cognitive impairment (SVCI). However, little is known about the pattern of CBF reduction in relation with the degree of cognitive impairment. CBF measured with three-dimensional (3D) Arterial Spin Labeling (ASL) perfusion magnetic resonance imaging (MRI) helps detect functional changes in subjects with SVCI. We aimed to compare CBF maps in subcortical ischemic vascular disease (SIVD) subjects with and without cognitive impairment and to detect the relationship of the regions of CBF reduction in the brain with the degree of cognitive impairment according to the z-score. A total of 53 subjects with SVCI and 23 matched SIVD subjects without cognitive impairment (controls), underwent a whole-brain 3D ASL MRI in the resting state. Regional CBF (rCBF) was compared voxel wise by using an analysis of variance design in a statistical parametric mapping program, with patient age and sex as covariates. Correlations were calculated between the rCBF value in the whole brain and the z-score in the 53 subjects with SVCI. Compared with the control subjects, SVCI group demonstrated diffuse decreased CBF in the brain. Significant positive correlations were determined in the rCBF values in the left hippocampus, left superior temporal pole gyrus, right superior frontal orbital lobe, right medial frontal orbital lobe, right middle temporal lobe, left thalamus and right insula with the z-scores in SVCI group. The noninvasively quantified resting CBF demonstrated altered CBF distributions in the SVCI brain. The deficit brain perfusions in the temporal and frontal lobe, hippocampus, thalamus and insula was related to the degree of cognitive impairment. Its relationship to cognition indicates the clinical relevance of this functional marker. Thus, our results provide further evidence for the mechanisms underlying the cognitive deficit in patients with SVCI. PMID:27630562

  6. Using fMRI non-local means denoising to uncover activation in sub-cortical structures at 1.5 T for guided HARDI tractography.

    PubMed

    Bernier, Michaël; Chamberland, Maxime; Houde, Jean-Christophe; Descoteaux, Maxime; Whittingstall, Kevin

    2014-01-01

    In recent years, there has been ever-increasing interest in combining functional magnetic resonance imaging (fMRI) and diffusion magnetic resonance imaging (dMRI) for better understanding the link between cortical activity and connectivity, respectively. However, it is challenging to detect and validate fMRI activity in key sub-cortical areas such as the thalamus, given that they are prone to susceptibility artifacts due to the partial volume effects (PVE) of surrounding tissues (GM/WM interface). This is especially true on relatively low-field clinical MR systems (e.g., 1.5 T). We propose to overcome this limitation by using a spatial denoising technique used in structural MRI and more recently in diffusion MRI called non-local means (NLM) denoising, which uses a patch-based approach to suppress the noise locally. To test this, we measured fMRI in 20 healthy subjects performing three block-based tasks : eyes-open closed (EOC) and left/right finger tapping (FTL, FTR). Overall, we found that NLM yielded more thalamic activity compared to traditional denoising methods. In order to validate our pipeline, we also investigated known structural connectivity going through the thalamus using HARDI tractography: the optic radiations, related to the EOC task, and the cortico-spinal tract (CST) for FTL and FTR. To do so, we reconstructed the tracts using functionally based thalamic and cortical ROIs to initiates seeds of tractography in a two-level coarse-to-fine fashion. We applied this method at the single subject level, which allowed us to see the structural connections underlying fMRI thalamic activity. In summary, we propose a new fMRI processing pipeline which uses a recent spatial denoising technique (NLM) to successfully detect sub-cortical activity which was validated using an advanced dMRI seeding strategy in single subjects at 1.5 T.

  7. Subcortical hyperintensity volumetrics in Alzheimer’s disease and normal elderly in the Sunnybrook Dementia Study: correlations with atrophy, executive function, mental processing speed, and verbal memory

    PubMed Central

    2014-01-01

    Introduction Subcortical hyperintensities (SHs) are radiological entities commonly observed on magnetic resonance imaging (MRI) of patients with Alzheimer’s disease (AD) and normal elderly controls. Although the presence of SH is believed to indicate some form of subcortical vasculopathy, pathological heterogeneity, methodological differences, and the contribution of brain atrophy associated with AD pathology have yielded inconsistent results in the literature. Methods Using the Lesion Explorer (LE) MRI processing pipeline for SH quantification and brain atrophy, this study examined SH volumes of interest and cognitive function in a sample of patients with AD (n = 265) and normal elderly controls (n = 100) from the Sunnybrook Dementia Study. Results Compared with healthy controls, patients with AD were found to have less gray matter, less white matter, and more sulcal and ventricular cerebrospinal fluid (all significant, P <0.0001). Additionally, patients with AD had greater volumes of whole-brain SH (P <0.01), periventricular SH (pvSH) (P <0.01), deep white SH (dwSH) (P <0.05), and lacunar lesions (P <0.0001). In patients with AD, regression analyses revealed a significant association between global atrophy and pvSH (P = 0.02) and ventricular atrophy with whole-brain SH (P <0.0001). Regional volumes of interest revealed significant correlations with medial middle frontal SH volume and executive function (P <0.001) in normal controls but not in patients with AD, global pvSH volume and mental processing speed (P <0.01) in patients with AD, and left temporal SH volume and memory (P <0.01) in patients with AD. Conclusions These brain-behavior relationships and correlations with brain atrophy suggest that subtle, yet measurable, signs of small vessel disease may have potential clinical relevance as targets for treatment in Alzheimer’s dementia. PMID:25478020

  8. Education modifies the relation of vascular pathology to cognitive function: cognitive reserve in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.

    PubMed

    Zieren, Nikola; Duering, Marco; Peters, Nils; Reyes, Sonia; Jouvent, Eric; Hervé, Dominique; Gschwendtner, Andreas; Mewald, Yvonne; Opherk, Christian; Chabriat, Hugues; Dichgans, Martin

    2013-02-01

    A clinical impact of cognitive reserve (CR) has been demonstrated in Alzheimer's disease, whereas its role in vascular cognitive impairment (VCI) is largely unknown. In this study, we investigated the impact of CR in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a genetic variant of pure VCI. A total of 247 NOTCH3 mutation carriers from a two-center study were investigated using detailed neuropsychological and neuroimaging protocols. CR was operationalized as years of formal education. Brain pathology was assessed by MRI using normalized brain volume and lacunar lesion volume as proxies. Multivariate analyses were done for each structural measure with scores of processing speed, executive function, and memory as dependent variables. Additional linear regression models were conducted with interaction terms for education × brain volume and education × lacunar lesion volume. Education had an independent impact on cognitive performance in subjects with mild and moderate degrees of brain pathology, whereas there was no significant influence of education on cognition in patients with severe MRI changes. This interaction was found for processing speed, the cognitive domain most impaired in our patients. Our findings demonstrate an interaction of education and brain pathology in regard to cognitive impairment: the effect of education seems most pronounced in early disease stages but may ultimately be overwhelmed by the pathological changes. The results extend the concept of CR to VCI.

  9. [A case of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) in which lomerizine hydrochloride was suggested to prevent recurrent stroke].

    PubMed

    Shimizu, Hisao; Nagami, Shuhei; Takahashi, Nobuyuki

    2014-01-01

    A 60-year-old man visited our hospital because of left hemiparesis in September 2006. Magnetic resonance imaging (MRI) revealed a high-intensity lesions in the right corona radiata on diffusion-weighted images and a high-intensity lesions in the basal ganglia and deep white matter on T2-weighted images. He recovered with no sequelae. Antithrombotic agents such as aspirin were given to prevent stroke, but stroke recurred three times over the course of 3 years. In February 2009, neurological examination revealed right hemiparalysis and dysarthria. Dysphagia and cognitive decline had been progressing gradually. We suspected cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) on the basis of the clinical and family history. An Arg75Pro mutation in the Notch3 gene was found, but did not involve a cysteine residue. Antithrombotic agents were ineffective. We tried lomerizine hydrochloride, which was reported to prevent stroke in a patient with CADASIL. In Japan, lomerizine hydrochloride is used to prevent migraine and to selectively inhibit cerebral artery contraction. During treatment with lomerizine hydrochloride (5 mg/day) for more than 3 years, there was no recurrence of cerebral infarction and no further deterioration of cognitive function or MRI findings. There is no evidence supporting the efficacy of antithrombotic agents in CADASIL patients. Moreover, antithrombotic agents have been reported to increase the frequency of clinically silent microbleeds on MRI in CADASIL. Lomerizine hydrochloride might therefore be one option for the treatment of CADASIL.

  10. The Gothenburg MCI study: Design and distribution of Alzheimer’s disease and subcortical vascular disease diagnoses from baseline to 6-year follow-up

    PubMed Central

    Nordlund, Arto; Jonsson, Michael; Lind, Karin; Edman, Åke; Göthlin, Mattias; Stålhammar, Jacob; Eckerström, Marie; Kern, Silke; Börjesson-Hanson, Anne; Carlsson, Mårten; Olsson, Erik; Zetterberg, Henrik; Blennow, Kaj; Svensson, Johan; Öhrfelt, Annika; Bjerke, Maria; Rolstad, Sindre; Eckerström, Carl

    2016-01-01

    There is a need for increased nosological knowledge to enable rational trials in Alzheimer’s disease (AD) and related disorders. The ongoing Gothenburg mild cognitive impairment (MCI) study is an attempt to conduct longitudinal in-depth phenotyping of patients with different forms and degrees of cognitive impairment using neuropsychological, neuroimaging, and neurochemical tools. Particular attention is paid to the interplay between AD and subcortical vascular disease, the latter representing a disease entity that may cause or contribute to cognitive impairment with an effect size that may be comparable to AD. Of 664 patients enrolled between 1999 and 2013, 195 were diagnosed with subjective cognitive impairment (SCI), 274 with mild cognitive impairment (MCI), and 195 with dementia, at baseline. Of the 195 (29%) patients with dementia at baseline, 81 (42%) had AD, 27 (14%) SVD, 41 (21%) mixed type dementia (=AD + SVD = MixD), and 46 (23%) other etiologies. After 6 years, 292 SCI/MCI patients were eligible for follow-up. Of these 292, 69 (24%) had converted to dementia (29 (42%) AD, 16 (23%) SVD, 15 (22%) MixD, 9 (13%) other etiologies). The study has shown that it is possible to identify not only AD but also incipient and manifest MixD/SVD in a memory clinic setting. These conditions should be taken into account in clinical trials. PMID:26174331

  11. A high resolution and high contrast MRI for differentiation of subcortical structures for DBS targeting: the Fast Gray Matter Acquisition T1 Inversion Recovery (FGATIR).

    PubMed

    Sudhyadhom, Atchar; Haq, Ihtsham U; Foote, Kelly D; Okun, Michael S; Bova, Frank J

    2009-08-01

    DBS depends on precise placement of the stimulating electrode into an appropriate target region. Image-based (direct) targeting has been limited by the ability of current technology to visualize DBS targets. We have recently developed and employed a Fast Gray Matter Acquisition T1 Inversion Recovery (FGATIR) 3T MRI sequence to more reliably visualize these structures. The FGATIR provides significantly better high resolution thin (1 mm) slice visualization of DBS targets than does either standard 3T T1 or T2-weighted imaging. The T1 subcortical image revealed relatively poor contrast among the targets for DBS, though the sequence did allow localization of striatum and thalamus. T2 FLAIR scans demonstrated better contrast between the STN, SNr, red nucleus (RN), and pallidum (GPe/GPi). The FGATIR scans allowed for localization of the thalamus, striatum, GPe/GPi, RN, and SNr and displayed sharper delineation of these structures. The FGATIR also revealed features not visible on other scan types: the internal lamina of the GPi, fiber bundles from the internal capsule piercing the striatum, and the boundaries of the STN. We hope that use of the FGATIR to aid initial targeting will translate in future studies to faster and more accurate procedures with consequent improvements in clinical outcomes.

  12. Decreased Subcortical and Increased Cortical Degree Centrality in a Nonclinical College Student Sample with Subclinical Depressive Symptoms: A Resting-State fMRI Study

    PubMed Central

    Gao, Cuihua; Wenhua, Liu; Liu, Yanli; Ruan, Xiuhang; Chen, Xin; Liu, Lingling; Yu, Shaode; Chan, Raymond C. K.; Wei, Xinhua; Jiang, Xinqing

    2016-01-01

    Abnormal functional connectivity (FC) at rest has been identified in clinical depressive disorder. However, very few studies have been conducted to understand the underlying neural substrates of subclinical depression. The newly proposed centrality analysis approach has been increasingly used to explore the large-scale brain network of mental diseases. This study aimed to identify the degree centrality (DC) alteration of the brain network in subclinical depressive subjects. Thirty-seven candidates with subclinical depression and 34 well-matched healthy controls (HCs) were recruited from the same sample of college students. All subjects underwent a resting-state fMRI (rs-fMRI) scan to assess the DC of the whole brain. Compared with controls, subclinical depressive subjects displayed decreased DC in the right parahippocampal gyrus (PHG), left PHG/amygdala, and left caudate and elevated DC in the right posterior parietal lobule (PPL), left inferior frontal gyrus (IFG) and left middle frontal gyrus (MFG). In addition, by using receiver operating characteristic (ROC) analysis, we determined that the DC values in the regions with altered FC between the two groups can be used to differentiate subclinical depressive subjects from HCs. We suggest that decreased DC in subcortical and increased DC in cortical regions might be the neural substrates of subclinical depression. PMID:27994546

  13. Coordinated Recruitment of Cortical-Subcortical Circuits and Ascending Dopamine and Serotonin Neurons During Inhibitory Control of Cocaine Seeking in Rats.

    PubMed

    Navailles, Sylvia; Guillem, Karine; Vouillac-Mendoza, Caroline; Ahmed, Serge H

    2015-09-01

    People with cocaine addiction retain some degree of prefrontal cortex (PFC) inhibitory control of cocaine craving, a brain capacity that may underlie the efficacy of cognitive behavioral therapy for addiction. Similar findings were recently found in rats after extended access to and escalation of cocaine self-administration. Rats' inhibitory control of cocaine seeking was flexible, sufficiently strong to suppress cocaine-primed reinstatement and depended, at least in part, on neuronal activity within the prelimbic (PL) PFC. Here, we used a large-scale and high-resolution Fos mapping approach to identify, beyond the PL PFC, how top-down and/or bottom-up PFC-subcortical circuits are recruited during inhibition of cocaine seeking. Overall, we found that effective inhibitory control of cocaine seeking is associated with the coordinated recruitment of different top-down cortical-striatal circuits originating from different PFC territories, and of different bottom-up dopamine (DA) and serotonin (5-HT) midbrain subsystems that normally modulate activity in these circuits. This integrated brain response suggests that rats concomitantly engage and experience intricate cognitive and affective processes when they have to inhibit intense cocaine seeking. Thus, even after extended drug use, rats can be successfully trained to engage whole-brain inhibitory control mechanisms to suppress cocaine seeking.

  14. Open and closed cortico-subcortical loops: A neuro-computational account of access to consciousness in the distractor-induced blindness paradigm.

    PubMed

    Ebner, Christian; Schroll, Henning; Winther, Gesche; Niedeggen, Michael; Hamker, Fred H

    2015-09-01

    How the brain decides which information to process 'consciously' has been debated over for decades without a simple explanation at hand. While most experiments manipulate the perceptual energy of presented stimuli, the distractor-induced blindness task is a prototypical paradigm to investigate gating of information into consciousness without or with only minor visual manipulation. In this paradigm, subjects are asked to report intervals of coherent dot motion in a rapid serial visual presentation (RSVP) stream, whenever these are preceded by a particular color stimulus in a different RSVP stream. If distractors (i.e., intervals of coherent dot motion prior to the color stimulus) are shown, subjects' abilities to perceive and report intervals of target dot motion decrease, particularly with short delays between intervals of target color and target motion. We propose a biologically plausible neuro-computational model of how the brain controls access to consciousness to explain how distractor-induced blindness originates from information processing in the cortex and basal ganglia. The model suggests that conscious perception requires reverberation of activity in cortico-subcortical loops and that basal-ganglia pathways can either allow or inhibit this reverberation. In the distractor-induced blindness paradigm, inadequate distractor-induced response tendencies are suppressed by the inhibitory 'hyperdirect' pathway of the basal ganglia. If a target follows such a distractor closely, temporal aftereffects of distractor suppression prevent target identification. The model reproduces experimental data on how delays between target color and target motion affect the probability of target detection.

  15. Patient assessment based on a theory of visual attention (TVA): subtle deficits after a right frontal-subcortical lesion.

    PubMed

    Habekost, Thomas; Bundesen, Claus

    2003-01-01

    We report on a patient who complained of reduced awareness in the left visual field, but showed no visual neglect or extinction in clinical testing. By MR scanning, the brain damage was localized to the right basal ganglia, also involving structures in right frontal cortex. Using psychophysical testing and mathematical modeling based on Bundesen's theory of visual attention [TVA; Psychol. Rev. 97 (1990) 523], the patient's subjective experience of attentional disturbance was confirmed, and the deficit was specified into several components. At very short exposure durations, two effects were shown. The detection threshold was elevated, particularly in the left visual field, and stimuli in this side were given less attentional weight. In addition, the capacity of visual short-term memory (VSTM) was markedly reduced in both visual fields. The robustness of the test results was evaluated by bootstrap analysis. The study demonstrates the sensitivity and specificity gained by combining psychophysical testing with TVA modeling in the analysis of visual attention disorders. Extending the results of a pioneer study of parietal neglect patients by Duncan et al. [J. Exp. Psychol.: Gen. 128 (1999) 450], this study demonstrates the strength of the method in a single case, with a lesion outside parietal cortex, and only minor clinical symptoms.

  16. Risk and Determinants of Dementia in Patients with Mild Cognitive Impairment and Brain Subcortical Vascular Changes: A Study of Clinical, Neuroimaging, and Biological Markers—The VMCI-Tuscany Study: Rationale, Design, and Methodology

    PubMed Central

    Poggesi, Anna; Salvadori, Emilia; Pantoni, Leonardo; Pracucci, Giovanni; Cesari, Francesca; Chiti, Alberto; Ciolli, Laura; Cosottini, Mirco; Del Bene, Alessandra; De Stefano, Nicola; Diciotti, Stefano; Dotti, Maria Teresa; Ginestroni, Andrea; Giusti, Betti; Gori, Anna Maria; Nannucci, Serena; Orlandi, Giovanni; Pescini, Francesca; Valenti, Raffaella; Abbate, Rosanna; Federico, Antonio; Mascalchi, Mario; Murri, Luigi; Inzitari, Domenico

    2012-01-01

    Dementia is one of the most disabling conditions. Alzheimer's disease and vascular dementia (VaD) are the most frequent causes. Subcortical VaD is consequent to deep-brain small vessel disease (SVD) and is the most frequent form of VaD. Its pathological hallmarks are ischemic white matter changes and lacunar infarcts. Degenerative and vascular changes often coexist, but mechanisms of interaction are incompletely understood. The term mild cognitive impairment defines a transitional state between normal ageing and dementia. Pre-dementia stages of VaD are also acknowledged (vascular mild cognitive impairment, VMCI). Progression relates mostly to the subcortical VaD type, but determinants of such transition are unknown. Variability of phenotypic expression is not fully explained by severity grade of lesions, as depicted by conventional MRI that is not sensitive to microstructural and metabolic alterations. Advanced neuroimaging techniques seem able to achieve this. Beside hypoperfusion, blood-brain-barrier dysfunction has been also demonstrated in subcortical VaD. The aim of the Vascular Mild Cognitive Impairment Tuscany Study is to expand knowledge about determinants of transition from mild cognitive impairment to dementia in patients with cerebral SVD. This paper summarizes the main aims and methodological aspects of this multicenter, ongoing, observational study enrolling patients affected by VMCI with SVD. PMID:22550606

  17. Immunolocalization of platelet‐derived growth factor receptor‐β (PDGFR‐β) and pericytes in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)

    PubMed Central

    Fenwick, Richard; Oakley, Arthur E.; Ihara, Masafumi

    2015-01-01

    Aims Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is identified by aggregates of NOTCH3 extracellular domain (N3ECD) along capillaries and the deposition of granular osmiophilic material (GOM). We assessed the pattern of distribution of pericytes in relation to N3ECD deposits in cerebral microvessels of CADASIL subjects. Methods We assessed post mortem brains from (n = 50) subjects with CADASIL, cerebral small vessel disease, and similar‐age cognitively normal and older controls. Immunohistochemical and immunofluorescent staining methods were used to study the distribution and quantify immunoreactivities of the platelet‐derived growth factor receptor‐β (PDGFR‐β) (for pericytes) and microvascular markers in the frontal cortex and white matter. Results PDGFR‐β antibody stained cells typical of pericytes in capillaries and small arterioles in both the grey and white matter. PDGFR‐β reactive pericytes adopted ‘crescent’ morphology wrapped closely around capillary walls readily evident in cross‐sections. We noted considerable overlap between PDGFR‐β and N3ECD imunoreactivities in capillaries. Quantitative analysis of PDGFR‐β immunoreactivity revealed significant differences in PDGFR‐β %A in CADASIL compared with young controls (P < 0.05). PDGFR‐β %A was further positively correlated with the basement membrane marker collagen IV (r = 0.529, P = 0.009), but was not associated with GLUT‐1, the marker for endothelial cells. Conclusions Our results suggest increased expression of PDGFR‐β immunoreactive pericytes in cerebral microvessels in CADASIL compared with similar age controls. While we cannot confirm whether PDGFR‐β‐expressing pericytes produce N3ECD and hence GOM, our findings demonstrate that up‐regulation of pericyte‐like cells is associated with microvascular changes, including loss of vascular smooth muscle cells in CADASIL. PMID:25303037

  18. Lewy Bodies, Vascular Risk Factors, and Subcortical Arteriosclerotic Leukoencephalopathy, but not Alzheimer Pathology, are Associated with Development of Psychosis in Alzheimer’s Disease

    PubMed Central

    Fischer, Corinne E.; Qian, Winnie; Schweizer, Tom A.; Millikin, Colleen P.; Ismail, Zahinoor; Smith, Eric E.; Lix, Lisa M.; Shelton, Paul; Munoz, David G.

    2016-01-01

    Background The neuropathological correlates of psychosis in Alzheimer’s disease (AD) is unclear, with some studies reporting a correlation between psychosis and increased AD pathology while others have found no association. Objective To determine the demographic, clinical, and neuropathological features associated with psychotic symptoms in clinically attributed and neuropathologically proven AD. Method We separately reviewed two overlapping groups of clinically diagnosed (cAD) AD patients with neuropathology data and neuropathologically definite (npAD) cases (regardless of clinical diagnosis) from the NACC database, and explored the relationships between psychosis and clinical variables, neuropathologic correlates, and vascular risk factors. Delusions and hallucinations, defined according to the NPI-Q, were analyzed separately. Results 1,073 subjects in the database fulfilled our criteria (890 cAD and 728 npAD patients). 34% of cAD and 37% of npAD had psychotic symptoms during their illness. Hallucinations were associated with greater cognitive and functional impairments on the MMSE and CDR, while delusional patients showed less impairment on CDR, consistent across cAD and npAD groups. Burden of AD pathology appears to relate to presence of psychotic symptoms in the clinical AD group, but this result is not confirmed in the neuropathologically confirmed group suggesting the findings in the clinical group were due to misdiagnosis of AD. Lewy body pathology, subcortical arteriosclerotic leukoencephalopathy, and vascular risk factors, including a history of hypertension and diabetes, were associated with the development of psychosis. Conclusions Vascular and Lewy body pathologies and vascular risk factors are important modifiers of the risk of psychosis in AD. PMID:26682680

  19. Can Blood Pressure Be Lowered Safely in Older Adults with Lacunar Stroke? The Secondary Prevention of Small Subcortical Strokes Study Experience

    PubMed Central

    White, Carole L.; Szychowski, Jeff M.; Pergola, Pablo E.; Field, Thalia S.; Talbert, Robert; Lau, Helena; Peri, Kalyani; Benavente, Oscar R.

    2015-01-01

    OBJECTIVES To determine safety and tolerability of lowering blood pressure in older adults with lacunar stroke. DESIGN Cohort study. SETTING The Secondary Prevention of Small Subcortical Strokes (SPS3) Trial, which compared the efficacy of two systolic blood pressure (SBP) targets (<130 mmHg and 130–149 mmHg) for secondary stroke prevention. PARTICIPANTS Of 3,020 SPS3 participants, 494 aged 75 and older at baseline were used in these analyses. MEASUREMENTS Rates of side effects related to lowering SBP and clinical outcomes, including stroke recurrence and vascular death, were examined. RESULTS Older participants achieved SBP levels similar to those of younger participants (mean SBP of 125 mmHg and 137 mmHg in lower and higher SBP target groups, respectively). At least once during the approximately 3.5 years of follow-up, 21% reported dizziness, and 15% reported lightheadedness when standing; the only significant difference between the younger and older groups was unsteadiness when standing (23% vs 32% respectively, P < .001). There was no difference according to treatment group. In younger adults, recurrent stroke was less likely in the lower than the higher SBP group (hazard ratio (HR) = 0.77, 95% confidence interval (CI) = 0.59–1.01) but not in older participants (HR = 1.01, 95% CI = 0.59– 1.73), although the interaction was not significant (P = .39). The lower SBP target was associated with a significant reduction in vascular death in older participants (HR = 0.42, 95% CI = 0.18–0.98), with a significant interaction between age and SBP group (P = .049). CONCLUSION Except for unsteadiness when standing, there was no difference according to age in individuals with lacunar stroke with respect to side effects potentially related to lowering blood pressure. Although the lower SBP target was not associated with lower likelihood of recurrent stroke, these exploratory analyses suggested a possible benefit related to vascular death. PMID:25850462

  20. Extended Broca's area in the functional connectome of language in adults: combined cortical and subcortical single-subject analysis using fMRI and DTI tractography.

    PubMed

    Lemaire, Jean-Jacques; Golby, Alexandra; Wells, William M; Pujol, Sonia; Tie, Yanmei; Rigolo, Laura; Yarmarkovich, Alexander; Pieper, Steve; Westin, Carl-Fredrik; Jolesz, Ferenc; Kikinis, Ron

    2013-07-01

    Traditional models of the human language circuitry encompass three cortical areas, Broca's, Geschwind's and Wernicke's, and their connectivity through white matter fascicles. The neural connectivity deep to these cortical areas remains poorly understood, as does the macroscopic functional organization of the cortico-subcortical language circuitry. In an effort to expand current knowledge, we combined functional MRI (fMRI) and diffusion tensor imaging to explore subject-specific structural and functional macroscopic connectivity, focusing on Broca's area. Fascicles were studied using diffusion tensor imaging fiber tracking seeded from volumes placed manually within the white matter. White matter fascicles and fMRI-derived clusters (antonym-generation task) of positive and negative blood-oxygen-level-dependent (BOLD) signal were co-registered with 3-D renderings of the brain in 12 healthy subjects. Fascicles connecting BOLD-derived clusters were analyzed within specific cortical areas: Broca's, with the pars triangularis, the pars opercularis, and the pars orbitaris; Geschwind's and Wernicke's; the premotor cortex, the dorsal supplementary motor area, the middle temporal gyrus, the dorsal prefrontal cortex and the frontopolar region. We found a functional connectome divisible into three systems-anterior, superior and inferior-around the insula, more complex than previously thought, particularly with respect to a new extended Broca's area. The extended Broca's area involves two new fascicles: the operculo-premotor fascicle comprised of well-organized U-shaped fibers that connect the pars opercularis with the premotor region; and (2) the triangulo-orbitaris system comprised of intermingled U-shaped fibers that connect the pars triangularis with the pars orbitaris. The findings enhance our understanding of language function.

  1. Ketamine Dysregulates the Amplitude and Connectivity of High-Frequency Oscillations in Cortical–Subcortical Networks in Humans: Evidence From Resting-State Magnetoencephalography-Recordings

    PubMed Central

    Rivolta, Davide; Heidegger, Tonio; Scheller, Bertram; Sauer, Andreas; Schaum, Michael; Birkner, Katharina; Singer, Wolf; Wibral, Michael; Uhlhaas, Peter J.

    2015-01-01

    Hypofunctioning of the N-methyl-D-aspartate receptor (NMDA-R) has been prominently implicated in the pathophysiology of schizophrenia (ScZ). The current study tested the effects of ketamine, a dissociative anesthetic and NMDA-R antagonist, on resting-state activity recorded with magnetoencephalography (MEG) in healthy volunteers. In a single-blind cross-over design, each participant (n = 12) received, on 2 different sessions, a subanesthetic dose of S-ketamine (0.006mg/Kg) and saline injection. MEG-data were analyzed at sensor- and source-level in the beta (13–30 Hz) and gamma (30–90 Hz) frequency ranges. In addition, connectivity analysis at source-level was performed using transfer entropy (TE). Ketamine increased gamma-power while beta-band activity was decreased. Specifically, elevated 30–90 Hz activity was pronounced in subcortical (thalamus and hippocampus) and cortical (frontal and temporal cortex) regions, whilst reductions in beta-band power were localized to the precuneus, cerebellum, anterior cingulate, temporal and visual cortex. TE analysis demonstrated increased information transfer in a thalamo-cortical network after ketamine administration. The findings are consistent with the pronounced dysregulation of high-frequency oscillations following the inhibition of NMDA-R in animal models of ScZ as well as with evidence from electroencephalogram-data in ScZ-patients and increased functional connectivity during early illness stages. Moreover, our data highlight the potential contribution of thalamo-cortical connectivity patterns towards ketamine-induced neuronal dysregulation, which may be relevant for the understanding of ScZ as a disorder of disinhibition of neural circuits. PMID:25987642

  2. Ketamine Dysregulates the Amplitude and Connectivity of High-Frequency Oscillations in Cortical-Subcortical Networks in Humans: Evidence From Resting-State Magnetoencephalography-Recordings.

    PubMed

    Rivolta, Davide; Heidegger, Tonio; Scheller, Bertram; Sauer, Andreas; Schaum, Michael; Birkner, Katharina; Singer, Wolf; Wibral, Michael; Uhlhaas, Peter J

    2015-09-01

    Hypofunctioning of the N-methyl-D-aspartate receptor (NMDA-R) has been prominently implicated in the pathophysiology of schizophrenia (ScZ). The current study tested the effects of ketamine, a dissociative anesthetic and NMDA-R antagonist, on resting-state activity recorded with magnetoencephalography (MEG) in healthy volunteers. In a single-blind cross-over design, each participant (n = 12) received, on 2 different sessions, a subanesthetic dose of S-ketamine (0.006 mg/Kg) and saline injection. MEG-data were analyzed at sensor- and source-level in the beta (13-30 Hz) and gamma (30-90 Hz) frequency ranges. In addition, connectivity analysis at source-level was performed using transfer entropy (TE). Ketamine increased gamma-power while beta-band activity was decreased. Specifically, elevated 30-90 Hz activity was pronounced in subcortical (thalamus and hippocampus) and cortical (frontal and temporal cortex) regions, whilst reductions in beta-band power were localized to the precuneus, cerebellum, anterior cingulate, temporal and visual cortex. TE analysis demonstrated increased information transfer in a thalamo-cortical network after ketamine administration. The findings are consistent with the pronounced dysregulation of high-frequency oscillations following the inhibition of NMDA-R in animal models of ScZ as well as with evidence from electroencephalogram-data in ScZ-patients and increased functional connectivity during early illness stages. Moreover, our data highlight the potential contribution of thalamo-cortical connectivity patterns towards ketamine-induced neuronal dysregulation, which may be relevant for the understanding of ScZ as a disorder of disinhibition of neural circuits.

  3. Subcortical anarthria: a case report.

    PubMed

    Ure, J; Morasso, C; Funes, J; Ollari, J; Videla, H; Diez, M

    2001-07-01

    A 56-year-old right-handed male with a history of hypertension and diabetes presented two episodes of stroke: The first affected territory was the left anterior coroidal artery (capsular and paracapsular infarcts at the level of the genu and posterior arm of the internal capsule) and the second was the right thalamus, due to a hematoma. Following the first stroke, the patient developed severe dysarthria and after the second stroke remained anarthric. The pathophysiology of the disorder is discussed, and the role of the left and right thalamus as far as speech is concerned is reviewed.

  4. Ten Novel Mutations in Chinese Patients with Megalencephalic Leukoencephalopathy with Subcortical Cysts and a Long-Term Follow-Up Research

    PubMed Central

    Cao, Binbin; Yan, Huifang; Guo, Mangmang; Xie, Han; Wu, Ye; Gu, Qiang; Xiao, Jiangxi; Shang, Jing; Yang, Yanling; Xiong, Hui; Niu, Zhengping; Wu, Xiru; Jiang, Yuwu; Wang, Jingmin

    2016-01-01

    Objective Megalencephalic leukoencephalopathy with subcortical cysts (MLC, OMIM 604004) is a rare neurological deterioration disease. We aimed to clarify clinical and genetic features of Chinese MLC patients. Methods Clinical information and peripheral venous blood of 20 patients and their families were collected, Sanger-sequencing and Multiple Ligation-dependent Probe Amplification were performed to make genetic analysis. Splicing-site mutation was confirmed with RT-PCR. UPD was detected by haplotype analysis. Follow-up study was performed through telephone for 27 patients. Results Out of 20 patients, macrocephaly, classic MRI features, motor development delay and cognitive impairment were detected in 20(100%), 20(100%), 17(85%) and 4(20%) patients, respectively. 20(100%) were clinically diagnosed with MLC. 19(95%) were genetically diagnosed with 10 novel mutations in MLC1, MLC1 and GlialCAM mutations were identified in 15 and 4 patients, respectively. Deletion mutation from exon4 to exon9 and a homozygous point mutation due to maternal UPD of chromosome22 in MLC1 were found firstly. c.598-2A>C in MLC1 leads to the skip of exon8. c.772-1G>C in MLC1 accounting for 15.5%(9/58) alleles in Chinese patients might be a founder or a hot-spot mutation. Out of 27 patients in the follow-up study, head circumference was ranged from 56cm to 61cm in patients older than 5yeas old, with a median of 57cm. Motor development delay and cognitive impairment were detected in 22(81.5%) and 5(18.5%) patients, respectively. Motor and cognitive deterioration was found in 5 (18.5%) and 2 patients (7.4%), respectively. Improvements and MRI recovery were first found in Chinese patients. Rate of seizures (45.5%), transient motor retrogress (45.5%) and unconsciousness (13.6%) after head trauma was much higher than that after fever (18.2%, 9.1%, 0%, respectively). Significance It’s a clinical and genetic analysis and a follow-up study for largest sample of Chinese MLC patients, identifying 10

  5. IMP1, an mRNA binding protein that reduces the metastatic potential of breast cancer in a mouse model

    PubMed Central

    Nwokafor, Chiso U.; Sellers, Rani S.; Singer, Robert H.

    2016-01-01

    Cells that are able to localize β-actin mRNA efficiently have decreased metastatic potential. Invasive carcinoma cells derived from primary mammary tumors have reduced levels of an RNA binding protein IMP1/ZBP1/IGF2BP1, required for β-actin mRNA localization. We showed previously that in human breast carcinoma cells in vitro, this protein suppresses invasion. In this work we examined whether its re-expression can suppress breast cancer metastasis in a breast cancer mouse model. We developed a mouse conditionally expressing IMP1-GFP (hereinafter referred to as the IMP1 transgene) specifically in the mammary gland of a PYMT breast cancer mouse. We found that mice conditionally expressing the IMP1 transgene showed little or no metastases to the lungs from the primary tumor in contrast to PYMT mice not expressing IMP1, which uniformly develop metastases at an early stage. PMID:27655671

  6. Re-appraising contemporary theories of subcortical participation in language: proposing an interhemispheric regulatory function for the subthalamic nucleus (STN) in the mediation of high-level linguistic processes.

    PubMed

    Whelan, Brooke-Mai; Murdoch, Bruce E; Theodoros, Deborah; Silburn, Peter; Hall, Bruce

    2004-10-01

    Apropos the basal ganglia, the dominant striatum and globus pallidus internus (GPi) have been hypothesized to represent integral components of subcortical language circuitry. Working subcortical language theories, however, have failed thus far to consider a role for the STN in the mediation of linguistic processes, a structure recently defined as the driving force of basal ganglia output. The aim of this research was to investigate the impact of surgically induced functional inhibition of the STN upon linguistic abilities, within the context of established models of basal ganglia participation in language. Two males with surgically induced'lesions'of the dominant and non-dominant dorsolateral STN, aimed at relieving Parkinsonian motor symptoms, served as experimental subjects. General and high-level language profiles were compiled for each subject up to 1 month prior to and 3 months following neurosurgery, within the drug-on state (i.e., when optimally medicated). Comparable post-operative alterations in linguistic performance were observed subsequent to surgically induced functional inhibition of the left and right STN. More specifically, higher proportions of reliable decline as opposed to improvement in post-operative performance were demonstrated by both subjects on complex language tasks, hypothesised to entail the interplay of cognitive-linguistic processes. The outcomes of the current research challenge unilateralised models of functional basal ganglia organisation with the proposal of a potential interhemispheric regulatory function for the STN in the mediation of high-level linguistic processes.

  7. Reduced Regional Brain Cortical Thickness in Patients with Heart Failure

    PubMed Central

    Kumar, Rajesh; Yadav, Santosh K.; Palomares, Jose A.; Park, Bumhee; Joshi, Shantanu H.; Ogren, Jennifer A.; Macey, Paul M.; Fonarow, Gregg C.; Harper, Ronald M.; Woo, Mary A.

    2015-01-01

    Aims Autonomic, cognitive, and neuropsychologic deficits appear in heart failure (HF) subjects, and these compromised functions depend on cerebral cortex integrity in addition to that of subcortical and brainstem sites. Impaired autoregulation, low cardiac output, sleep-disordered-breathing, hypertension, and diabetic conditions in HF offer considerable potential to affect cortical areas by loss of neurons and glia, which would be expressed as reduced cortical thicknesses. However, except for gross descriptions of cortical volume loss/injury, regional cortical thickness integrity in HF is unknown. Our goal was to assess regional cortical thicknesses across the brain in HF, compared to control subjects. Methods and Results We examined localized cortical thicknesses in 35 HF and 61 control subjects with high-resolution T1-weighted images (3.0-Tesla MRI) using FreeSurfer software, and assessed group differences with analysis-of-covariance (covariates; age, gender; p<0.05; FDR). Significantly-reduced cortical thicknesses appeared in HF over controls in multiple areas, including the frontal, parietal, temporal, and occipital lobes, more markedly on the left side, within areas that control autonomic, cognitive, affective, language, and visual functions. Conclusion Heart failure subjects show reduced regional cortical thicknesses in sites that control autonomic, cognitive, affective, language, and visual functions that are deficient in the condition. The findings suggest chronic tissue alterations, with regional changes reflecting loss of neurons and glia, and presumably are related to earlier-described axonal changes. The pathological mechanisms contributing to reduced cortical thicknesses likely include hypoxia/ischemia, accompanying impaired cerebral perfusion from reduced cardiac output and sleep-disordered-breathing and other comorbidities in HF. PMID:25962164

  8. Reduce HIV Risk

    MedlinePlus

    ... incidence could be reduced if people changed their sexual behaviors. Our research has demonstrated remarkable success in reducing HIV risk-associated sexual behaviors among African American adolescents and adults." Spring 2008 ...

  9. Reducing Teacher Incompetence.

    ERIC Educational Resources Information Center

    Rich, John Martin

    1988-01-01

    Suggests how administrators may reduce teacher incompetence. Teacher incompetence can be reduced if administrators fully understand and undertake appropriate preventive and remedial measures. Two sections comprise this article. First, a taxonomy of teacher incompetence reveals the magnitude of the problem. Second, preventive and remedial measures…

  10. Reducible oxide based catalysts

    DOEpatents

    Thompson, Levi T.; Kim, Chang Hwan; Bej, Shyamal K.

    2010-04-06

    A catalyst is disclosed herein. The catalyst includes a reducible oxide support and at least one noble metal fixed on the reducible oxide support. The noble metal(s) is loaded on the support at a substantially constant temperature and pH.

  11. Detection of complement factor B in the cerebrospinal fluid of patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy disease using two-dimensional gel electrophoresis and mass spectrometry.

    PubMed

    Unlü, M; de Lange, R P; de Silva, R; Kalaria, R; St Clair, D

    2000-03-24

    Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary condition with onset in mid-adulthood and is associated with mutations in the Notch-3 gene. (Joutel, A., Corepechot, C., Ducros, A., Vahedi, K., Chabriat, H., Mouton, P., Alamowitch, S., Domenda, V., Cecilion, M., Marechal, J., Vayssiere, C., Cruaud, C., Cabanis, E.A., Ruchoux, M.M. , Weissenvach, J., Bach, J.F., Bousser, M.G. and Tournier-Lasserve, E., Notch3 mutations in CADASIL, a hereditary adult-onset condition causing stroke and dementia. Nature, 383 (1996) 707-710) Ultrastructural examination of the pathology of the cerebral infarcts reveals deposits in the vascular smooth muscle cells of the small arteries of the brain, but there is no obvious indication how the Notch-3 mutations give rise the observed pathology, nor is there any information on the exact nature of the deposits. We have investigated cerebrospinal fluid (CSF) from three CADASIL cases with known mutations in Notch-3 using two-dimensional gel electrophoresis. CSF from these patients was compared to that of six controls. We detected a single spot in the protein maps of patients which was absent from all the controls. In-gel tryptic digestion of this protein followed by mass spectrometric analysis of the tryptic fragments and a database search identified the spot as human complement factor B. These preliminary findings suggest that the alternative complement pathway may play a role in the pathogenesis of CADASIL.

  12. [Are subcortical signs in the EEG a reliable indication of brain stem displacement and impaction processes by intracranial space-occupying processes? A comparative computer tomography-electroencephalography study].

    PubMed

    Zettler, H; Järisch, M; Leonhard, T

    1985-01-01

    Within the scope of an elektroencephalographic-computertomographic comperative study carried out in 430 patients, the concurrence of secondary brain stem damage due to mass displacement and herniation processes and parroxysmal generalised slow activity in the EEG ("intermittant frontal delta rhythms", "projected discharges", "subcortical signs") in intracranial space-occupying processes were studied among others. The occurrence of the EEG pattern was independent of the presence of brain stem displacements in about 20 and 25 per cent, respectively, of the 152 patients with supratentorial space occupations. The absence of the characteristics on 80 per cent of the patients with clear CT criteria for a secondary brain stem impairment shows that it is not suitable as a warning sign of an imminent intracranial decompensation and that in particular from the non-occurrence in the EEG no contribution to the operative risk and to the choice of the time of the operation can be derived. A relation between the occurrence of paroxysmal slow activity and the acuity of the course of the disease or the degree of malignity of cerebral tumours could not be verified. Possible causes of the inconstant occurrence of this EEG pattern in brain stem alterations are discussed.

  13. High-resolution nuclear magnetic resonance imaging and single photon emission computerized tomography--cerebral blood flow in a case of pure sensory stroke and mild dementia owing to subcortical arteriosclerotic encephalopathy (Binswanger's disease)

    SciTech Connect

    De Chiara, S.; Lassen, N.A.; Andersen, A.R.; Gade, A.; Lester, J.; Thomsen, C.; Henriksen, O.

    1987-01-01

    Pure sensory stroke (PSS) is typically caused by a lacunar infarct located in the ventral-posterior (VP) thalamic nucleus contralateral to the paresthetic symptoms. The lesion is usually so small that it cannot be seen on computerized tomography (CT), as illustrated by our case. In our moderately hypertensive, 72-year-old patient with PSS, CT scanning and conventional nuclear magnetic resonance imaging (NMRI) scanning using a 7-mm-thick slice on a 1.5 Tesla instrument all failed to visualize the thalamic infarct. Using the high-resolution mode with 2-mm slice thickness it was, however, clearly seen. In addition, NMRI unexpectedly showed diffuse periventricular demyelinization as well as three other lacunar infarcts, i.e., findings characteristic of subcortical arteriosclerotic encephalopathy (SAE). This prompted psychometric testing, which revealed signs of mild (subclinical) dementia, in particular involving visiospatial apraxia; this pointed to decreased function of the right parietal cortex, which was structurally intact on CT and NMRI. Single photon emission computerized tomography by Xenon-133 injection and by hexamethyl-propyleneamine-oxim labeled with Technetium-99m showed asymmetric distribution of cerebral blood flow (CBF), with an 18% lower value in the right parietal cortex compared to the left side; this indicated asymmetric disconnection of the cortex by the SAE. Thus, the tomograms of the functional parameter, CBF, correlated better with the deficits revealed by neuropsychological testing than by CT or NMRI.

  14. Reducing Childhood Obesity

    MedlinePlus

    ... Navigation Bar Home Current Issue Past Issues Reducing Childhood Obesity Past Issues / Summer 2007 Table of Contents For ... page please turn Javascript on. The We Can! childhood obesity-prevention program involves parents, caregivers, and community leaders ...

  15. Reduced shear power spectrum

    SciTech Connect

    Dodelson, Scott; Shapiro, Charles; White, Martin J.; /UC, Berkeley, Astron. Dept. /UC, Berkeley

    2005-08-01

    Measurements of ellipticities of background galaxies are sensitive to the reduced shear, the cosmic shear divided by (1-{kappa}) where {kappa} is the projected density field. They compute the difference between shear and reduced shear both analytically and with simulations. The difference becomes more important an smaller scales, and will impact cosmological parameter estimation from upcoming experiments. A simple recipe is presented to carry out the required correction.

  16. Reduced Magmatic Volatiles

    NASA Astrophysics Data System (ADS)

    Hirschmann, M. M.; Withers, A. C.; Ardia, P.; Stanley, B. D.; Foley, N.

    2012-12-01

    Volatiles in Earth's upper mantle are dominated by H2O and CO2, but under more reduced conditions likely deeper in the mantle, other volatile species may be important or dominant. However, the speciation, solubilities, and effect on physical properties of reduced magmatic volatiles are poorly constrained. Here we summarize results from an experimental campaign to better understand reduced volatiles in magmas. Experiments emphasize spectroscopic and SIMS characterization of dissolved species in experiments for which fluid fugacities are known, thereby facilitating thermodynamic parameterization. Experimental determinations of molecular H2 solubility in basaltic and andesitic liquids show concentrations that are proportional to H2 fugacity. Because H2 increases with fH2 whereas dissolved H2O increases with fH2O1/2, the relative importance of H2 increases with pressure and for more hydrous magmas. At 1 GPa and IW-1, solubility in basalt reaches 0.3 wt.% (equivalent to 2.7 wt.% H2O). Solubilities at pressures of the deep upper mantle have not been explored experimentally (as is also true for H2O and CO2), but H2 could become the dominant hydrous species at 400 km and deeper, and so deep hydrous melts may have chiefly H2 rather than H2O or OH. Experiments suggest an extremely low partial specific density (0.18 kg/m3) for dissolved H2 at low pressure, and so appreciable dissolved H2 in melt atop the 410 km discontinuity or in the lower mantle may promote positive buoyancy. Solubilities of reduced C-species remain poorly known. In contrast to results in Na2O-SiO2 liquids (Mysen et al., 2009), experiments with a haplobasaltic liquid at controlled CH4 fugacities indicated very small (<0.05 wt.%) CH4 solubilities even at very reduced conditions (reduced conditions and in

  17. Reduced volume of the nucleus accumbens in heroin addiction.

    PubMed

    Seifert, Christian L; Magon, Stefano; Sprenger, Till; Lang, Undine E; Huber, Christian G; Denier, Niklaus; Vogel, Marc; Schmidt, André; Radue, Ernst-Wilhelm; Borgwardt, Stefan; Walter, Marc

    2015-12-01

    The neural mechanisms of heroin addiction are still incompletely understood, even though modern neuroimaging techniques offer insights into disease-related changes in vivo. While changes on cortical structure have been reported in heroin addiction, evidence from subcortical areas remains underrepresented. Functional imaging studies revealed that the brain reward system and particularly the nucleus accumbens (NAcc) play a pivotal role in the pathophysiology of drug addiction. The aim of this study was to investigate whether there was a volume difference of the NAcc in heroin addiction in comparison to healthy controls. A further aim was to correlate subcortical volumes with clinical measurements on negative affects in addiction. Thirty heroin-dependent patients under maintenance treatment with diacetylmorphine and twenty healthy controls underwent structural MRI scanning at 3T. Subcortical segmentation analysis was performed using FMRIB's Integrated Registration and Segmentation Tool function of FSL. The State-Trait Anxiety Inventory and the Beck Depression Inventory were used to assess trait anxiety and depressive symptoms, respectively. A decreased volume of the left NAcc was observed in heroin-dependent patients compared to healthy controls. Depression score was negatively correlated with left NAcc volume in patients, whereas a positive correlation was found between the daily opioid dose and the volume of the right amygdala. This study indicates that there might be structural differences of the NAcc in heroin-dependent patients in comparison with healthy controls. Furthermore, correlations of subcortical structures with negative emotions and opioid doses might be of future relevance for the investigation of heroin addiction.

  18. Reduced Amygdalar Gray Matter Volume in Familial Pediatric Bipolar Disorder

    ERIC Educational Resources Information Center

    Chang, Kiki; Karchemskiy, Asya; Barnea-Goraly, Naama; Garrett, Amy; Simeonova, Diana Iorgova; Reiss, Allan

    2005-01-01

    Objective: Subcortical limbic structures have been proposed to be involved in the pathophysiology of adult and pediatric bipolar disorder (BD). We sought to study morphometric characteristics of these structures in pediatric subjects with familial BD compared with healthy controls. Method: Twenty children and adolescents with BD I (mean age = 14.6…

  19. Tank closure reducing grout

    SciTech Connect

    Caldwell, T.B.

    1997-04-18

    A reducing grout has been developed for closing high level waste tanks at the Savannah River Site in Aiken, South Carolina. The grout has a low redox potential, which minimizes the mobility of Sr{sup 90}, the radionuclide with the highest dose potential after closure. The grout also has a high pH which reduces the solubility of the plutonium isotopes. The grout has a high compressive strength and low permeability, which enhances its ability to limit the migration of contaminants after closure. The grout was designed and tested by Construction Technology Laboratories, Inc. Placement methods were developed by the Savannah River Site personnel.

  20. Prefrontal Transcranial Direct Current Stimulation Alters Activation and Connectivity in Cortical and Subcortical Reward Systems: A tDCS-fMRI Study

    PubMed Central

    Weber, Matthew J.; Messing, Samuel B.; Rao, Hengyi; Detre, John A.; Thompson-Schill, Sharon L.

    2014-01-01

    Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique used both experimentally and therapeutically to modulate regional brain function. However, few studies have directly measured the aftereffects of tDCS on brain activity or examined changes in task-related brain activity consequent to prefrontal tDCS. To investigate the neural effects of tDCS, we collected fMRI data from 22 human subjects, both at rest and while performing the Balloon Analog Risk Task (BART), before and after true or sham transcranial direct current stimulation. TDCS decreased resting blood perfusion in orbitofrontal cortex and the right caudate and increased task-related activity in the right dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) in response to losses but not wins or increasing risk. Network analysis showed that whole-brain connectivity of the right ACC correlated positively with the number of pumps subjects were willing to make on the BART, and that tDCS reduced connectivity between the right ACC and the rest of the brain. Whole-brain connectivity of the right DLPFC also correlated negatively with pumps on the BART, as prior literature would suggest. Our results suggest that tDCS can alter activation and connectivity in regions distal to the electrodes. PMID:24453107

  1. Reducing Behavior through Reinforcement.

    ERIC Educational Resources Information Center

    Deitz, Diane E. D.; Repp, Alan C.

    1983-01-01

    The use of reinforcement to reduce inappropriate behaviors of mentally retarded and emotionally disturbed students may involve the following procedures: differential reinforcement of low rates of responding (DRL), the differential reinforcement of response omission (DRO), and the differential reinforcement of incompatible (DRI) or alternative…

  2. Please Reduce Cycle Time

    DTIC Science & Technology

    2014-12-01

    Defense AT&L: November–December 2014 4 Please Reduce Cycle Time Brian Schultz “Time is what we want most but what we use worst.” — William Penn ...Schultz is a professor of program management at the Defense Acquisition University’s Mid-Atlantic Region in California, Md. As William Penn noted

  3. Reduced Braginskii equations

    SciTech Connect

    Yagi, M.; Horton, W. )

    1994-07-01

    A set of reduced Braginskii equations is derived without assuming flute ordering and the Boussinesq approximation. These model equations conserve the physical energy. It is crucial at finite [beta] that the perpendicular component of Ohm's law be solved to ensure [del][center dot][bold j]=0 for energy conservation.

  4. Demonstrating Reduced Gravity

    NASA Technical Reports Server (NTRS)

    Pearlman, Howard; Stocker, Dennis; Gotti, Daniel; Urban, David; Ross, Howard; Sours, Thomas

    1996-01-01

    A miniature drop tower, Reduced-Gravity Demonstrator is developed to illustrate the effects of gravity on a variety of phenomena including the way fluids flow, flames burn, and mechanical systems (such as pendulum) behave. A schematic and description of the demonstrator and payloads are given, followed by suggestions for how one can build his (her) own.

  5. Reduced density of glutamine synthetase immunoreactive astrocytes in different cortical areas in major depression but not in bipolar I disorder

    PubMed Central

    Bernstein, Hans-Gert; Meyer-Lotz, Gabriela; Dobrowolny, Henrik; Bannier, Jana; Steiner, Johann; Walter, Martin; Bogerts, Bernhard

    2015-01-01

    There is increasing evidence for disturbances within the glutamate system in patients with affective disorders, which involve disruptions of the glutamate–glutamine-cycle. The mainly astroglia-located enzyme glutamine synthetase (GS) catalyzes the ATP-dependent condensation of ammonia and glutamate to form glutamine, thus playing a central role in glutamate and glutamine homoeostasis. However, GS is also expressed in numerous oligodendrocytes (OLs), another class of glial cells implicated in mood disorder pathology. To learn more about the role of glia-associated GS in mental illnesses, we decided to find out if numerical densities of glial cells immunostained for the enzyme protein differ between subjects with major depressive disorder, bipolar disorder (BD), and psychically healthy control cases. Counting of GS expressing astrocytes (ACs) and OLs in eight cortical and two subcortical brain regions of subjects with mood disorder (N = 14), BD (N = 15), and controls (N = 16) revealed that in major depression the densities of ACs were significantly reduced in some cortical but not subcortical gray matter areas, whereas no changes were found for OLs. In BD no alterations of GS-immunoreactive glia were found. From our findings we conclude that (1) GS expressing ACs are prominently involved in glutamate-related disturbances in major depression, but not in BD and (2) GS expressing OLs, though being present in significant numbers in prefrontal cortical areas, play a minor (if any) role in mood disorder pathology. The latter assumption is supported by findings of others showing that – at least in the mouse brain cortex – GS immunoreactive oligodendroglial cells are unable to contribute to the glutamate–glutamine-cycle due to the complete lack of amino acid transporters (Takasaki et al., 2010). PMID:26321908

  6. Reduced density of glutamine synthetase immunoreactive astrocytes in different cortical areas in major depression but not in bipolar I disorder.

    PubMed

    Bernstein, Hans-Gert; Meyer-Lotz, Gabriela; Dobrowolny, Henrik; Bannier, Jana; Steiner, Johann; Walter, Martin; Bogerts, Bernhard

    2015-01-01

    There is increasing evidence for disturbances within the glutamate system in patients with affective disorders, which involve disruptions of the glutamate-glutamine-cycle. The mainly astroglia-located enzyme glutamine synthetase (GS) catalyzes the ATP-dependent condensation of ammonia and glutamate to form glutamine, thus playing a central role in glutamate and glutamine homoeostasis. However, GS is also expressed in numerous oligodendrocytes (OLs), another class of glial cells implicated in mood disorder pathology. To learn more about the role of glia-associated GS in mental illnesses, we decided to find out if numerical densities of glial cells immunostained for the enzyme protein differ between subjects with major depressive disorder, bipolar disorder (BD), and psychically healthy control cases. Counting of GS expressing astrocytes (ACs) and OLs in eight cortical and two subcortical brain regions of subjects with mood disorder (N = 14), BD (N = 15), and controls (N = 16) revealed that in major depression the densities of ACs were significantly reduced in some cortical but not subcortical gray matter areas, whereas no changes were found for OLs. In BD no alterations of GS-immunoreactive glia were found. From our findings we conclude that (1) GS expressing ACs are prominently involved in glutamate-related disturbances in major depression, but not in BD and (2) GS expressing OLs, though being present in significant numbers in prefrontal cortical areas, play a minor (if any) role in mood disorder pathology. The latter assumption is supported by findings of others showing that - at least in the mouse brain cortex - GS immunoreactive oligodendroglial cells are unable to contribute to the glutamate-glutamine-cycle due to the complete lack of amino acid transporters (Takasaki et al., 2010).

  7. Reducing float coal dust

    PubMed Central

    Patts, J.R.; Colinet, J.F.; Janisko, S.J.; Barone, T.L.; Patts, L.D.

    2016-01-01

    Controlling float coal dust in underground coal mines before dispersal into the general airstream can reduce the risk of mine explosions while potentially achieving a more effective and efficient use of rock dust. A prototype flooded-bed scrubber was evaluated for float coal dust control in the return of a continuous miner section. The scrubber was installed inline between the face ventilation tubing and an exhausting auxiliary fan. Airborne and deposited dust mass measurements were collected over three days at set distances from the fan exhaust to assess changes in float coal dust levels in the return due to operation of the scrubber. Mass-based measurements were collected on a per-cut basis and normalized on the basis of per ton mined by the continuous miner. The results show that average float coal dust levels measured under baseline conditions were reduced by more than 90 percent when operating the scrubber. PMID:28018004

  8. Reducing rotor weight

    SciTech Connect

    Cheney, M.C.

    1997-12-31

    The cost of energy for renewables has gained greater significance in recent years due to the drop in price in some competing energy sources, particularly natural gas. In pursuit of lower manufacturing costs for wind turbine systems, work was conducted to explore an innovative rotor designed to reduce weight and cost over conventional rotor systems. Trade-off studies were conducted to measure the influence of number of blades, stiffness, and manufacturing method on COE. The study showed that increasing number of blades at constant solidity significantly reduced rotor weight and that manufacturing the blades using pultrusion technology produced the lowest cost per pound. Under contracts with the National Renewable Energy Laboratory and the California Energy Commission, a 400 kW (33m diameter) turbine was designed employing this technology. The project included tests of an 80 kW (15.5m diameter) dynamically scaled rotor which demonstrated the viability of the design.

  9. Screening for Very Mild Subcortical Vascular Dementia Patients Aged 75 and Above Using the Montreal Cognitive Assessment and Mini-Mental State Examination in a Community: The Kurihara Project

    PubMed Central

    Kasai, Mari; Meguro, Kenichi; Nakamura, Kei; Nakatsuka, Masahiro; Ouchi, Yoshitaka; Tanaka, Naofumi

    2012-01-01

    Aims To examine the effectiveness of the Montreal Cognitive Assessment (MoCA) to screen people with mild cognitive impairment (MCI), to associate the MoCA score with the presence of infarction, and to detect the characteristics of people with very mild subcortical vascular dementia (vmSVD). Methods 392 out of 886 community dwellers aged 75 years and above living in Kurihara, Northern Japan, agreed to participate in our study; 164 scored a Clinical Dementia Rating (CDR) of 0 (healthy), 184 scored a CDR of 0.5 (MCI) and 44 scored a CDR of 1+ (dementia). The participants scoring a CDR of 0.5 were divided into 2 subtypes: 37 had vmSVD and 147 had other types of dementia. The objective variables were the total MoCA, the MoCA subscale and the Mini-Mental State Examination (MMSE). Results There was a difference in the MoCA and MMSE scores between the 3 CDR groups. The MoCA score overlapped in participants with CDR 0 and 0.5. There were significant CDR effects, while there were no significant infarction effects for the MoCA and MMSE. vmSVD participants had lower scores on the total MoCA, the MoCA attention subscale and MMSE than healthy elderly people and participants with other types of dementia. Conclusion Our results suggested that MMSE performed rather well and that the MoCA is not superior to MMSE in MCI and vmSVD participants aged 75 and above in a community. PMID:23277783

  10. The β1 subunit of the Na,K-ATPase pump interacts with megalencephalic leucoencephalopathy with subcortical cysts protein 1 (MLC1) in brain astrocytes: new insights into MLC pathogenesis

    PubMed Central

    Brignone, Maria S.; Lanciotti, Angela; Macioce, Pompeo; Macchia, Gianfranco; Gaetani, Matteo; Aloisi, Francesca; Petrucci, Tamara C.; Ambrosini, Elena

    2011-01-01

    Megalencephalic leucoencephalopathy with subcortical cysts (MLC) is a rare congenital leucodystrophy caused by mutations in MLC1, a membrane protein of unknown function. MLC1 expression in astrocyte end-feet contacting blood vessels and meninges, along with brain swelling, fluid cysts and myelin vacuolation observed in MLC patients, suggests a possible role for MLC1 in the regulation of fluid and ion homeostasis and cellular volume changes. To identify MLC1 direct interactors and dissect the molecular pathways in which MLC1 is involved, we used NH2-MLC1 domain as a bait to screen a human brain library in a yeast two-hybrid assay. We identified the β1 subunit of the Na,K-ATPase pump as one of the interacting clones and confirmed it by pull-downs, co-fractionation assays and immunofluorescence stainings in human and rat astrocytes in vitro and in brain tissue. By performing ouabain-affinity chromatography on astrocyte and brain extracts, we isolated MLC1 and the whole Na,K-ATPase enzyme in a multiprotein complex that included Kir4.1, syntrophin and dystrobrevin. Because Na,K-ATPase is involved in intracellular osmotic control and volume regulation, we investigated the effect of hypo-osmotic stress on MLC1/Na,K-ATPase relationship in astrocytes. We found that hypo-osmotic conditions increased MLC1 membrane expression and favoured MLC1/Na,K-ATPase-β1 association. Moreover, hypo-osmosis induced astrocyte swelling and the reversible formation of endosome-derived vacuoles, where the two proteins co-localized. These data suggest that through its interaction with Na,K-ATPase, MLC1 is involved in the control of intracellular osmotic conditions and volume regulation in astrocytes, opening new perspectives for understanding the pathological mechanisms of MLC disease. PMID:20926452

  11. Neurons in Vulnerable Regions of the Alzheimer's Disease Brain Display Reduced ATM Signaling.

    PubMed

    Shen, Xuting; Chen, Jianmin; Li, Jiali; Kofler, Julia; Herrup, Karl

    2016-01-01

    Ataxia telangiectasia (A-T) is a multisystemic disease caused by mutations in the ATM (A-T mutated) gene. It strikes before 5 years of age and leads to dysfunctions in many tissues, including the CNS, where it leads to neurodegeneration, primarily in cerebellum. Alzheimer's disease (AD), by contrast, is a largely sporadic neurodegenerative disorder that rarely strikes before the 7th decade of life with primary neuronal losses in hippocampus, frontal cortex, and certain subcortical nuclei. Despite these differences, we present data supporting the hypothesis that a failure of ATM signaling is involved in the neuronal death in individuals with AD. In both, partially ATM-deficient mice and AD mouse models, neurons show evidence for a loss of ATM. In human AD, three independent indices of reduced ATM function-nuclear translocation of histone deacetylase 4, trimethylation of histone H3, and the presence of cell cycle activity-appear coordinately in neurons in regions where degeneration is prevalent. These same neurons also show reduced ATM protein levels. And though they represent only a fraction of the total neurons in each affected region, their numbers significantly correlate with disease stage. This previously unknown role for the ATM kinase in AD pathogenesis suggests that the failure of ATM function may be an important contributor to the death of neurons in AD individuals.

  12. Reducing teenage pregnancy.

    PubMed

    Fallon, Debbie

    2011-03-01

    The Teenage Pregnancy Independent Advisory Group (TPIAG) was established in 2000 to advise the government about reducing teenage pregnancy rates and supporting teenage parents to continue with their education. The group reached the end of its tenure in December 2010. This short article highlights some of the key issues from the final report and provides some insights into past achievements and future directions from an interview with Gill Frances, TPIAG's chair.

  13. Gradual extinction reduces reinstatement

    PubMed Central

    Shiban, Youssef; Wittmann, Jasmin; Weißinger, Mara; Mühlberger, Andreas

    2015-01-01

    The current study investigated whether gradually reducing the frequency of aversive stimuli during extinction can prevent the return of fear. Thirty-one participants of a three-stage procedure (acquisition, extinction and a reinstatement test on day 2) were randomly assigned to a standard extinction (SE) and gradual extinction (GE) procedure. The two groups differed only in the extinction procedure. While the SE group ran through a regular extinction process without any negative events, the frequency of the aversive stimuli during the extinction phase was gradually reduced for the GE group. The unconditioned stimulus (US) was an air blast (5 bar, 10 ms). A spider and a scorpion were used as conditioned stimuli (CS). The outcome variables were contingency ratings and physiological measures (skin conductance response, SCR and startle response). There were no differences found between the two groups for the acquisition and extinction phases concerning contingency ratings, SCR, or startle response. GE compared to SE significantly reduced the return of fear in the reinstatement test for the startle response but not for SCR or contingency ratings. This study was successful in translating the findings in rodent to humans. The results suggest that the GE process is suitable for increasing the efficacy of fear extinction. PMID:26441581

  14. Reducing Iatrogenic Risks

    PubMed Central

    Ely, E. Wesley; Speroff, Theodore; Pun, Brenda T.; Boehm, Leanne; Dittus, Robert S.

    2010-01-01

    ICUs are experiencing an epidemic of patients with acute brain dysfunction (delirium) and weakness, both associated with increased mortality and long-term disability. These conditions are commonly acquired in the ICU and are often initiated or exacerbated by sedation and ventilation decisions and management. Despite > 10 years of evidence revealing the hazards of delirium, the quality chasm between current and ideal processes of care continues to exist. Monitoring of delirium and sedation levels remains inconsistent. In addition, sedation, ventilation, and physical therapy practices proven successful at reducing the frequency and severity of adverse outcomes are not routinely practiced. In this article, we advocate for the adoption and implementation of a standard bundle of ICU measures with great potential to reduce the burden of ICU-acquired delirium and weakness. Individual components of this bundle are evidence based and can help standardize communication, improve interdisciplinary care, reduce mortality, and improve cognitive and functional outcomes. We refer to this as the “ABCDE bundle,” for awakening and breathing coordination, delirium monitoring, and exercise/early mobility. This evidence-based bundle of practices will build a bridge across the current quality chasm from the “front end” to the “back end” of critical care and toward improved cognitive and functional outcomes for ICU survivors. PMID:21051398

  15. Naval electrochemical corrosion reducer

    DOEpatents

    Clark, Howard L.

    1991-10-01

    A corrosion reducer for use with ships having a hull, a propeller mounted a propeller shaft and extending through the hull, bearings supporting the shaft, at least one thrust bearing and one seal. The improvement includes a current collector and a current reduction assembly for reducing the voltage between the hull and shaft in order to reduce corrosion due to electrolytic action. The current reduction assembly includes an electrical contact, the current collector, and the hull. The current reduction assembly further includes a device for sensing and measuring the voltage between the hull and the shaft and a device for applying a reverse voltage between the hull and the shaft so that the resulting voltage differential is from 0 to 0.05 volts. The current reduction assembly further includes a differential amplifier having a voltage differential between the hull and the shaft. The current reduction assembly further includes an amplifier and a power output circuit receiving signals from the differential amplifier and being supplied by at least one current supply. The current selector includes a brush assembly in contact with a slip ring over the shaft so that its potential may be applied to the differential amplifier.

  16. Reducing Radiation Damage

    SciTech Connect

    Blankenbecler, Richard

    2006-06-05

    This talk describes the use of a modified treatment sequence, i.e., radiation dose, geometry, dwell time, etc., to mitigate some of the deleterious effects of cancer radiotherapy by utilizing natural cell repair processes. If bad side effects can be reduced, a more aggressive therapy can be put into place. Cells contain many mechanisms that repair damage of various types. If the damage can not be repaired, cells will undergo apoptosis (cell death). Data will be reviewed that support the fact that a small dose of radiation will activate damage repair genes within a cell. Once the mechanisms are fully active, they will efficiently repair the severe damage from a much larger radiation dose. The data ranges from experiments on specific cell cultures using microarray (gene chip) techniques to experiments on complete organisms. The suggested effect and treatment is consistent with the assumption that all radiation is harmful, no matter how small the dose. Nevertheless, the harm can be reduced. These mechanisms need to be further studied and characterized. In particular, their time dependence needs to be understood before the proposed treatment can be optimized. Under certain situations it is also possible that the deleterious effects of chemotherapy can be mitigated and the damage to radiation workers can be reduced.

  17. Coating Reduces Ice Adhesion

    NASA Technical Reports Server (NTRS)

    Smith, Trent; Prince, Michael; DwWeese, Charles; Curtis, Leslie

    2008-01-01

    The Shuttle Ice Liberation Coating (SILC) has been developed to reduce the adhesion of ice to surfaces on the space shuttle. SILC, when coated on a surface (foam, metal, epoxy primer, polymer surfaces), will reduce the adhesion of ice by as much as 90 percent as compared to the corresponding uncoated surface. This innovation is a durable coating that can withstand several cycles of ice growth and removal without loss of anti-adhesion properties. SILC is made of a binder composed of varying weight percents of siloxane(s), ethyl alcohol, ethyl sulfate, isopropyl alcohol, and of fine-particle polytetrafluoroethylene (PTFE). The combination of these components produces a coating with significantly improved weathering characteristics over the siloxane system alone. In some cases, the coating will delay ice formation and can reduce the amount of ice formed. SILC is not an ice prevention coating, but the very high water contact angle (greater than 140 ) causes water to readily run off the surface. This coating was designed for use at temperatures near -170 F (-112 C). Ice adhesion tests performed at temperatures from -170 to 20 F (-112 to -7 C) show that SILC is a very effective ice release coating. SILC can be left as applied (opaque) or buffed off until the surface appears clear. Energy dispersive spectroscopy (EDS) and x-ray photoelectron spectroscopy (XPS) data show that the coating is still present after buffing to transparency. This means SILC can be used to prevent ice adhesion even when coating windows or other objects, or items that require transmission of optical light. Car windshields are kept cleaner and SILC effectively mitigates rain and snow under driving conditions.

  18. Modelling reduced sparse data

    NASA Astrophysics Data System (ADS)

    Kozera, Ryszard; Noakes, Lyle

    2016-09-01

    In this paper we discuss the problem of fitting to an ordered collection of points in arbitary Euclidean space called reduced data. We are not given here the corresponding interpolation knots. Instead, these are estimated by new knots upon minimizing a relevant highly nonlinear optimization scheme based on natural spline interpolation. The existence of a global minimizer (i.e. the collection of interpolation knots in ascending order) is also addressed in this paper. Finally, Leap-Frog optimization tool is used to compute these knots approximating the unknown interpolation knots. This numerical scheme is subsequently compared with the Secant Method. Two illustrative examples are given.

  19. Nonlinearity-reduced interferometer

    NASA Astrophysics Data System (ADS)

    Wu, Chien-ming

    2007-12-01

    Periodic nonlinearity is a systematic error limiting the accuracy of displacement measurements at the nanometer level. It results from many causes such as the frequency mixing, polarization mixing, polarization-frequency mixing, and the ghost reflections. An interferometer having accuracy in displacement measurement of less than one-nanometer is necessary in nanometrology. To meet the requirement, the periodic nonlinearity should be less than deep sub-nanometer. In this paper, a nonlinearity-reduced interferometry has been proposed. Both the linear- and straightness-interferometer were tested. The developed interferometer demonstrated of a residual nonlinearity less than 25 pm.

  20. DNMT3B inhibits the re-expression of genes associated with induced pluripotency.

    PubMed

    Wongtrakoongate, Patompon; Li, Jianliang; Andrews, Peter W

    2014-02-15

    DNMT3B is a de novo DNA methyltransferase that is highly expressed in mouse and human embryonic stem (ES) cells and has been shown to be essential for differentiation of mouse ES cells toward different lineages. In the present study, we found that DNMT3B is rapidly down-regulated in human ES cells during retinoic acid (RA)-induced differentiation compared with DNMT3A2, which is also highly expressed in ES cells. Silencing of DNMT3B in human ES cells by an inducible shRNAi system leads to a reduction of clonal ability of the stem cells, while expression of OCT4 and NANOG is unchanged. By contrast, the germline-specific genes VASA and SCP3 and the surface antigen BE12 are down regulated following DNMT3B knockdown. Upon retinoic acid-induced differentiation, we found that depletion of DNMT3B leads to a decrease in expression of the surface antigen A2B5 and of neural tube-associated genes PAX7 and BRN3A. Consistent with its importance in stem cell differentiation, we observed that silencing of DNMT3B facilitates the generation of cells that bear the hallmarks of pluripotency. Our findings suggest a role of DNMT3B in controlling the differentiation of human ES cells and in the generation of iPS cells.

  1. Epigenetic re-expression of HIF-2α suppresses soft tissue sarcoma growth

    PubMed Central

    Nakazawa, Michael S.; Eisinger-Mathason, T. S. Karin; Sadri, Navid; Ochocki, Joshua D.; Gade, Terence P. F.; Amin, Ruchi K.; Simon, M. Celeste

    2016-01-01

    In soft tissue sarcomas (STS), low intratumoural O2 (hypoxia) is a poor prognostic indicator. HIF-1α mediates key transcriptional responses to hypoxia, and promotes STS metastasis; however, the role of the related HIF-2α protein is unknown. Surprisingly, here we show that HIF-2α inhibits high-grade STS cell growth in vivo, as loss of HIF-2α promotes sarcoma proliferation and increases calcium and mTORC1 signalling in undifferentiated pleomorphic sarcoma and dedifferentiated liposarcoma. We find that most human STS have lower levels of EPAS1 (the gene encoding HIF-2α) expression relative to normal tissue. Many cancers, including STS, contain altered epigenetics, and our findings define an epigenetic mechanism whereby EPAS1 is silenced during sarcoma progression. The clinically approved HDAC inhibitor Vorinostat specifically increases HIF-2α, but not HIF-1α, accumulation in multiple STS subtypes. Vorinostat inhibits STS tumour growth, an effect ameliorated by HIF-2α deletion, implicating HIF-2α as a biomarker for Vorinostat efficacy in STS. PMID:26837714

  2. Differentially methylated genes and androgen receptor re-expression in small cell prostate carcinomas.

    PubMed

    Kleb, Brittany; Estécio, Marcos R H; Zhang, Jiexin; Tzelepi, Vassiliki; Chung, Woonbok; Jelinek, Jaroslav; Navone, Nora M; Tahir, Salahaldin; Marquez, Victor E; Issa, Jean-Pierre; Maity, Sankar; Aparicio, Ana

    2016-03-03

    Small cell prostate carcinoma (SCPC) morphology is rare at initial diagnosis but often emerges during prostate cancer progression and portends a dismal prognosis. It does not express androgen receptor (AR) or respond to hormonal therapies. Clinically applicable markers for its early detection and treatment with effective chemotherapy are needed. Our studies in patient tumor-derived xenografts (PDX) revealed that AR-negative SCPC (AR(-)SCPC) expresses neural development genes instead of the prostate luminal epithelial genes characteristic of AR-positive castration-resistant adenocarcinomas (AR(+)ADENO). We hypothesized that the differences in cellular lineage programs are reflected in distinct epigenetic profiles. To address this hypothesis, we compared the DNA methylation profiles of AR(-) and AR(+) PDX using methylated CpG island amplification and microarray (MCAM) analysis and identified a set of differentially methylated promoters, validated in PDX and corresponding donor patient samples. We used the Illumina 450K platform to examine additional regions of the genome and the correlation between the DNA methylation profiles of the PDX and their corresponding patient tumors. Struck by the low frequency of AR promoter methylation in the AR(-)SCPC, we investigated this region's specific histone modification patterns by chromatin immunoprecipitation. We found that the AR promoter was enriched in silencing histone modifications (H3K27me3 and H3K9me2) and that EZH2 inhibition with 3-deazaneplanocin A (DZNep) resulted in AR expression and growth inhibition in AR(-)SCPC cell lines. We conclude that the epigenome of AR(-) is distinct from that of AR(+) castration-resistant prostate carcinomas, and that the AR(-) phenotype can be reversed with epigenetic drugs.

  3. Embodied intervention reduce depression

    NASA Astrophysics Data System (ADS)

    Song, Dong-Qing; Bi, Xin; Fu, Ying

    2011-10-01

    To investigate the difference of the selected-rate of undergraduates' depression with respect to time, gender and scales and the intervention effect of embodied exercise, 201 Undergraduates were measured with Self-Rating Depression Scale and Beck Depression Inventory (BDI).The result shows there are significant difference of the selected-rates of undergraduates' depression resulted from long-time interval rather than from short-time interval and gender. After the intervention, the selected-rates are decreased and no significant difference has been found between the embodied groups and the controlled group. Only the embodied groups maintain the better effects of the intervention in the tracking. Also the result shows that only the participants of embodied groups obtain more positive emotional experience. We conclude that there is significant difference of selected-rate of undergraduates' depression on scales, and the embodied exercise can effectively reduce undergraduate's depression.

  4. Reducing GWAS Complexity

    PubMed Central

    Hazelett, Dennis J.; Conti, David V.; Han, Ying; Al Olama, Ali Amin; Easton, Doug; Eeles, Rosalind A.; Kote-Jarai, Zsofia; Haiman, Christopher A.; Coetzee, Gerhard A.

    2016-01-01

    ABSTRACT Genome-wide association studies (GWAS) have revealed numerous genomic 'hits' associated with complex phenotypes. In most cases these hits, along with surrogate genetic variation as measure by numerous single nucleotide polymorphisms (SNPs) that are in linkage disequilibrium, are not in coding genes making assignment of functionality or causality intractable. Here we propose that fine-mapping along with the matching of risk SNPs at chromatin biofeatures lessen this complexity by reducing the number of candidate functional/causal SNPs. For example, we show here that only on average 2 SNPs per prostate cancer risk locus are likely candidates for functionality/causality; we further propose that this manageable number should be taken forward in mechanistic studies. The candidate SNPs can be looked up for each prostate cancer risk region in 2 recent publications in 20151,2 from our groups. PMID:26771711

  5. Pressure reducing regulator

    DOEpatents

    Whitehead, J.C.; Dilgard, L.W.

    1995-10-10

    A pressure reducing regulator that controls its downstream or outlet pressure to a fixed fraction of its upstream or inlet pressure is disclosed. The regulator includes a housing which may be of a titanium alloy, within which is located a seal or gasket at the outlet end which may be made of annealed copper, a rod, and piston, each of which may be made of high density graphite. The regulator is insensitive to temperature by virtue of being without a spring or gas sealed behind a diaphragm, and provides a reference for a system in which it is being used. The rod and piston of the regulator are constructed, for example, to have a 1/20 ratio such that when the downstream pressure is less than 1/20 of the upstream pressure the regulator opens and when the downstream pressure exceeds 1/20 of the upstream pressure the regulator closes. 10 figs.

  6. Pressure reducing regulator

    DOEpatents

    Whitehead, John C.; Dilgard, Lemoyne W.

    1995-01-01

    A pressure reducing regulator that controls its downstream or outlet pressure to a fixed fraction of its upstream or inlet pressure. The regulator includes a housing which may be of a titanium alloy, within which is located a seal or gasket at the outlet end which may be made of annealed copper, a rod, and piston, each of which may be made of high density graphite. The regulator is insensitive to temperature by virtue of being without a spring or gas sealed behind a diaphragm, and provides a reference for a system in which it is being used. The rod and piston of the regulator are constructed, for example, to have a 1/20 ratio such that when the downstream pressure is less than 1/20 of the upstream pressure the regulator opens and when the downstream pressure exceeds 1/20 of the upstream pressure the regulator closes.

  7. Reduced Order Podolsky Model

    NASA Astrophysics Data System (ADS)

    Thibes, Ronaldo

    2017-02-01

    We perform the canonical and path integral quantizations of a lower-order derivatives model describing Podolsky's generalized electrodynamics. The physical content of the model shows an auxiliary massive vector field coupled to the usual electromagnetic field. The equivalence with Podolsky's original model is studied at classical and quantum levels. Concerning the dynamical time evolution, we obtain a theory with two first-class and two second-class constraints in phase space. We calculate explicitly the corresponding Dirac brackets involving both vector fields. We use the Senjanovic procedure to implement the second-class constraints and the Batalin-Fradkin-Vilkovisky path integral quantization scheme to deal with the symmetries generated by the first-class constraints. The physical interpretation of the results turns out to be simpler due to the reduced derivatives order permeating the equations of motion, Dirac brackets and effective action.

  8. Reducing medical waste.

    PubMed

    Conrardy, Julie; Hillanbrand, Mary; Myers, Sandra; Nussbaum, George F

    2010-06-01

    Medical waste is a necessary by-product of any hospital environment; however, the majority of regulated medical waste is produced in the OR from the use of disposable surgical supplies (eg, drapes, gowns, basins, gloves, sponges). We conducted a concept comparison project in the ORs of two large medical centers in Bethesda, Maryland, and Washington, DC, to evaluate the effects of using reusable surgical basins, gowns, and table and Mayo stand covers in place of disposable products. Survey results indicated that surgeons and surgical technologists found the reusable products to be preferable to the disposable products currently in use. In addition, using reusable products provided a means to decrease regulated medical waste generated in the OR by an average of 65% as well as reduce the cost of waste disposal. AORN recommends evaluating the environmental effects of using reusable, reposable, and disposable products; our findings provide evidence that may be useful to surgical facilities that seek to adopt a "green" approach.

  9. Demyelination of subcortical nuclei in multiple sclerosis

    NASA Astrophysics Data System (ADS)

    Krutenkova, E.; Aitmagambetova, G.; Khodanovich, M.; Bowen, J.; Gangadharan, B.; Henson, L.; Mayadev, A.; Repovic, P.; Qian, P.; Yarnykh, V.

    2016-02-01

    Myelin containing in basal ganglia in multiple sclerosis patients was evaluated using new noninvasive quantitative MRI method fast whole brain macromolecular proton fraction mapping. Myelin level in globus pallidus and putamen significantly decreased in multiple sclerosis patients as compared with healthy control subjects but not in substantia nigra and caudate nucleus.

  10. Taking the High Road on Subcortical Transfer

    ERIC Educational Resources Information Center

    Miller, M.B.; Kingstone, A.

    2005-01-01

    Kingstone and Gazzaniga (1995) presented conceptually ambiguous word pairs, such as HOT-DOG, to a split-brain patient. Each hemisphere received only one of the words. With one hand, the patient drew the word pairs literally (e.g., a dog panting in the heat) but never drew the emergent object (e.g., a frankfurter in a bun). This finding suggested…

  11. Megalencephalic Leukoencephalopathy with Subcortical Cysts (MLC)

    MedlinePlus

    ... Us Name * First Last Email * Message Email This field is for validation purposes and should be left unchanged. Copyright © United Leukodystrophy Foundation, Inc. 224 North Second Street, Suite 2 DeKalb, Illinois USA. All rights ...

  12. Measuring the reduced shear

    NASA Astrophysics Data System (ADS)

    Zhang, Jun

    2011-11-01

    Neglecting the second order corrections in weak lensing measurements can lead to a few percent uncertainties on cosmic shears, and becomes more important for cluster lensing mass reconstructions. Existing methods which claim to measure the reduced shears are not necessarily accurate to the second order when a point spread function (PSF) is present. We show that the method of Zhang (2008) exactly measures the reduced shears at the second order level in the presence of PSF. A simple theorem is provided for further confirming our calculation, and for judging the accuracy of any shear measurement method at the second order based on its properties at the first order. The method of Zhang (2008) is well defined mathematically. It does not require assumptions on the morphologies of galaxies and the PSF. To reach a sub-percent level accuracy, the CCD pixel size is required to be not larger than 1/3 of the Full Width at Half Maximum (FWHM) of the PSF, regardless of whether the PSF has a power-law or exponential profile at large distances. Using a large ensemble (gtrsim107) of mock galaxies of unrestricted morphologies, we study the shear recovery accuracy under different noise conditions. We find that contaminations to the shear signals from the noise of background photons can be removed in a well defined way because they are not correlated with the source shapes. The residual shear measurement errors due to background noise are consistent with zero at the sub-percent level even when the amplitude of such noise reaches about 1/10 of the source flux within the half-light radius of the source. This limit can in principle be extended further with a larger galaxy ensemble in our simulations. On the other hand, the source Poisson noise remains to be a cause of systematic errors. For a sub-percent level accuracy, our method requires the amplitude of the source Poisson noise to be less than 1/80 ~ 1/100 of the source flux within the half-light radius of the source, corresponding to

  13. Measuring the reduced shear

    SciTech Connect

    Zhang, Jun

    2011-11-01

    Neglecting the second order corrections in weak lensing measurements can lead to a few percent uncertainties on cosmic shears, and becomes more important for cluster lensing mass reconstructions. Existing methods which claim to measure the reduced shears are not necessarily accurate to the second order when a point spread function (PSF) is present. We show that the method of Zhang (2008) exactly measures the reduced shears at the second order level in the presence of PSF. A simple theorem is provided for further confirming our calculation, and for judging the accuracy of any shear measurement method at the second order based on its properties at the first order. The method of Zhang (2008) is well defined mathematically. It does not require assumptions on the morphologies of galaxies and the PSF. To reach a sub-percent level accuracy, the CCD pixel size is required to be not larger than 1/3 of the Full Width at Half Maximum (FWHM) of the PSF, regardless of whether the PSF has a power-law or exponential profile at large distances. Using a large ensemble (∼>10{sup 7}) of mock galaxies of unrestricted morphologies, we study the shear recovery accuracy under different noise conditions. We find that contaminations to the shear signals from the noise of background photons can be removed in a well defined way because they are not correlated with the source shapes. The residual shear measurement errors due to background noise are consistent with zero at the sub-percent level even when the amplitude of such noise reaches about 1/10 of the source flux within the half-light radius of the source. This limit can in principle be extended further with a larger galaxy ensemble in our simulations. On the other hand, the source Poisson noise remains to be a cause of systematic errors. For a sub-percent level accuracy, our method requires the amplitude of the source Poisson noise to be less than 1/80 ∼ 1/100 of the source flux within the half-light radius of the source

  14. Pathogenic mutations associated with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy differently affect Jagged1 binding and Notch3 activity via the RBP/JK signaling Pathway.

    PubMed

    Joutel, Anne; Monet, Marie; Domenga, Valérie; Riant, Florence; Tournier-Lasserve, Elisabeth

    2004-02-01

    Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited vascular dementia characterized by the degeneration of smooth-muscle cells in small cerebral arteries. CADASIL is caused by mutations in NOTCH3, one of the four mammalian homologs to the Drosophila melanogaster NOTCH gene. Disease-associated mutations are distributed throughout the 34 epidermal growth factor-like repeats (EGFRs) that compose the extracellular domain of the Notch3 receptor and result in a loss or a gain of a cysteine residue in one of these EGFRs. In human adults, Notch3 expression is highly restricted to vascular smooth-muscle cells. In patients with CADASIL, there is an abnormal accumulation of Notch3 in the vessel. Molecular pathways linking NOTCH3 mutations to degeneration of vascular smooth-muscle cells are as yet poorly understood. In this study, we investigated the effect of CADASIL mutations on Notch3 activity. We studied five naturally occurring mutations: R90C and C212S, located in the previously identified mutational hotspot EGFR2-5; C428S, shown in this study to be located in the ligand-binding domain EGFR10-11; and C542Y and R1006C, located in EGFR13 and EGFR26, respectively. All five mutant proteins were correctly processed. The C428S and C542Y mutant receptors exhibited a significant reduction in Jagged1-induced transcriptional activity of a RBP/JK responsive luciferase reporter, relative to wild-type Notch3. Impaired signaling activity of these two mutants arose through different mechanisms; the C428S mutant lost its Jagged1-binding ability, whereas C542Y retained it but exhibited an impaired presentation to the cell surface. In contrast, the R90C, C212S, and R1006C mutants retained the ability to bind Jagged1 and were associated with apparently normal levels of signaling activity. We conclude that mutations in Notch3 differently affect Jagged1 binding and Notch3 signaling via the RBP/JK pathway.

  15. Stewarding a Reduced Stockpile

    SciTech Connect

    Goodwin, B T; Mara, G

    2008-04-18

    The future of the US nuclear arsenal continues to be guided by two distinct drivers: the preservation of world peace and the prevention of further proliferation through our extended deterrent umbrella. Timely implementation of US nuclear policy decisions depends, in part, on the current state of stockpile weapons, their delivery systems, and the supporting infrastructure within the Department of Defense (DoD) and the Department of Energy's National Nuclear Security Administration (NNSA). In turn, the present is a product of past choices and world events. Now more than ever, the nuclear weapons program must respond to the changing global security environment and to increasing budget pressures with innovation and sound investments. As the nation transitions to a reduced stockpile, the successes of the Stockpile Stewardship Program (SSP) present options to transition to a sustainable complex better suited to stockpile size, national strategic goals and budgetary realities. Under any stockpile size, we must maintain essential human capital, forefront capabilities, and have a right-sized effective production capacity. We present new concepts for maintaining high confidence at low stockpile numbers and to effectively eliminate the reserve weapons within an optimized complex. We, as a nation, have choices to make on how we will achieve a credible 21st century deterrent.

  16. Reducing miner absenteeism

    SciTech Connect

    Peters, R.H.; Clingan, M.R.; Randolph, R.F.

    1989-01-01

    The U. S. Bureau of Mines has prepared this report on strategies for maintaining high job attendance among underground coal miners because high absenteeism is a threat to miners' safety and seriously hampers productivity. A substantial number of research studies on the effectiveness of various strategies for reducing absenteeism among the employees of nonmining industries have been reported in the literature. These strategies have aimed at improving job attendance through one or more of the following: (1) improving employment procedures, (2) overcoming problems that adversely affect one's ability to attend work, and (3) increasing miners' motivation to attend work. Many of these strategies appear applicable to the mining industry, and are reviewed in the first half of this report. The second half of this report describes how one could develop and implement a program for maintaining high attendance at underground coal mines. The steps include measuring and evaluating attendance levels, formulating attendance goals and an absenteeism policy, developing and implementing an attendance promotion program and periodically going through the preceding steps (known as recycling).

  17. Pollution reducing aircraft propulsion

    SciTech Connect

    Tamura, R.

    1980-07-29

    An aircraft pollution reducing propulsion airfoil system comprising a wing having upper and lower surfaces comprising wing skin plates extending longitudinally on the wing and being spaced one from another in chordwise directions, spars extending into the wing between the surfaces, stringer ducts extending along internal sides of the wing surfaces, the stringers having relatively rigid surface-supporting structure and having outward directed openings extending across the wing surfaces, interrupting the wing surfaces between edges of the wing skin plates, the ducts thereby forming stringer structural elements supporting the wing skin plates, the outward directed openings of the stringer ducts being arranged perpendicularly to the wing surfaces in a leading portion of the wing and tangential to the wing surfaces in a trailing portion of the wing surfaces, suction means connected to the stringer ducts with perpendicular opening for drawing gas into the ducts through those openings and blowing means connected to the ducts with tangential openings for flowing gas out of the tangential openings, combustion means connected to the suction means and to the blowing meanas for accelerating gas through the means.

  18. Delayed fertilization of anuran amphibian (Xenopus) eggs leads to reduced numbers of primordial germ cells

    NASA Technical Reports Server (NTRS)

    Wakahara, M.; Neff, A. W.; Malacinski, G. M.

    1984-01-01

    Several media were tested for the extent to which they promoted high fertilization efficiencies in ovulated, stripped Xenopus eggs. One medium was selected for maintaining eggs in a 'delayed fertilization' (DelF) condition. DelF eggs displayed several unusual characteristics, including shift of the center of gravity, prominent sperm entrance site, and occasional polyspermy. The frequency of normal pattern formation varied according to the length of time eggs were maintained in the DelF condition. Various developmental abnormalities were observed during gastrulation, neurulation, and organogenesis. Most abnormalities appeared, however, to be related to morphogenesis of the endoderm. Primordial germ cell (PGC) development was examined in DelF eggs which displayed normal external morphological features at the swimming tadpole stage. PGC counts were usually normal in short-duration (eg, 5 hr) DelF eggs, but frequently substantially reduced or completely diminished in longer-duration (eg, 25h) tadpoles. Six spawnings were compared and shown to exhibit considerable variability in fertility, morphogenesis, and PGC development. Yolk platelet shifts and developmental parameters were examined in two additional spawnings. The subcortical cytoplasm in which the germ plasm is normally localized appeared to be disrupted in longer duration DelF eggs. That observation may account for low PGC counts in DelF tadpoles.

  19. Delayed fertilization of anuran amphibian (Xenopus) eggs leads to reduced numbers of primordial germ cells.

    PubMed

    Wakahara, M; Neff, A W; Malacinski, G M

    1984-01-01

    Several media were tested for the extent to which they promoted high fertilization efficiencies in ovulated, stripped Xenopus eggs. One medium was selected for maintaining eggs in a 'delayed fertilization' (DelF) condition. DelF eggs displayed several unusual characteristics, including shift of the center of gravity, prominent sperm entrance site, and occasional polyspermy. The frequency of normal pattern formation varied according to the length of time eggs were maintained in the DelF condition. Various developmental abnormalities were observed during gastrulation, neurulation, and organogenesis. Most abnormalities appeared, however, to be related to morphogenesis of the endoderm. Primordial germ cell (PGC) development was examined in DelF eggs which displayed normal external morphological features at the swimming tadpole stage. PGC counts were usually normal in short-duration (eg, 5 hr) DelF eggs, but frequently substantially reduced or completely diminished in longer-duration (eg, 25h) tadpoles. Six spawnings were compared and shown to exhibit considerable variability in fertility, morphogenesis, and PGC development. Yolk platelet shifts and developmental parameters were examined in two additional spawnings. The subcortical cytoplasm in which the germ plasm is normally localized appeared to be disrupted in longer duration DelF eggs. That observation may account for low PGC counts in DelF tadpoles.

  20. Reduced Gravity Walking Simulator

    NASA Technical Reports Server (NTRS)

    1963-01-01

    A test subject being suited up for studies on the Reduced Gravity Walking Simulator located in the hanger at Langley Research Center. The initial version of this simulator was located inside the hanger. Later a larger version would be located at the Lunar Landing Facility. The purpose of this simulator was to study the subject while walking, jumping or running. Researchers conducted studies of various factors such as fatigue limit, energy expenditure, and speed of locomotion. Francis B. Smith wrote in his paper 'Simulators For Manned Space Research,' 'I would like to conclude this talk with a discussion of a device for simulating lunar gravity which is very effective and yet which is so simple that its cost is in the order of a few thousand dollars at most, rather than hundreds of thousands. With a little ingenuity, one could almost build this type simulator in his backyard for children to play on. The principle is ...if a test subject is suspended in a sling so that his body axis makes an angle of 9 1/2 degrees with the horizontal and if he then 'stands' on a platform perpendicular to his body axis, the component of the earth's gravity forcing him toward the platform is one times the sine of 9 1/2 degrees or approximately 1/6 of the earth's normal gravity field. That is, a 180 pound astronaut 'standing' on the platform would exert a force of only 30 pounds - the same as if he were standing upright on the lunar surface.' Published in James R. Hansen, Spaceflight Revolution: NASA Langley Research Center From Sputnik to Apollo, NASA SP-4308; Francis B. Smith, 'Simulators For Manned Space Research,' Paper for 1966 IEEE International Convention, New York, NY, March 21-25, 1966.

  1. Reducing gas generators and methods for generating a reducing gas

    DOEpatents

    Scotto, Mark Vincent; Perna, Mark Anthony

    2015-11-03

    One embodiment of the present invention is a unique reducing gas generator. Another embodiment is a unique method for generating a reducing gas. Other embodiments include apparatuses, systems, devices, hardware, methods, and combinations for generating reducing gas. Further embodiments, forms, features, aspects, benefits, and advantages of the present application will become apparent from the description and figures provided herewith.

  2. Gene Variants Reduce Opioid Risks

    MedlinePlus

    ... this reduced potency is due to changes in binding to the receptor or to changes in the ... the body’s natural opioids, β-endorphin. Because this binding reduces the number of receptors required to achieve ...

  3. Reduced cortical responses to noxious heat in patients with rheumatoid arthritis

    PubMed Central

    Jones, A; Derbyshire, S

    1997-01-01

    OBJECTIVES—To test the hypothesis that patients with chronic inflammatory pain develop adaptive cortical responses to noxious stimulation characterised by reduced anterior cingulate responses.
METHODS—Positron emission tomography was used to measure changes in regional cerebral blood flow (rCBF) in response to an acute experimental pain stimulus in six patients with rheumatoid arthritis (RA) in comparison to six age and sex matched controls. A standardised and reproducible non-painful and painful phasic heat stimulus was delivered by a thermal probe to the back of the right hand during six two minute periods during which time rCBF measurements were made. The effects of non-painful heat were subtracted from those of painful heat to weight the analysis towards the non-discriminatory or `suffering' components of pain processing. Significance maps of pain processing were generated and compared in each group and contrasted with results obtained in a group of patients with atypical facial pain (AFP) that have been previously published.
RESULTS—The RA patients showed remarkably damped cortical and subcortical responses to pain compared with the control group. Significant differences between the two groups were observed in the prefrontal (BA 10) and anterior cingulate (BA 24 ) and cingulofrontal transition cortical (BA 32) areas. The reduced anterior cingulate responses to standardised heat pain were compared with the increased cingulate responses seen in patients with psychogenically maintained pain (AFP) who had both lower pain tolerance and mood than the RA group.
CONCLUSIONS—Major cortical adaptive responses to standardised noxious heat can be measured and contrasted in patients with different types of chronic pain. The different pattern of cingulate and frontal cortical responses in the patients with inflammatory and non-nociceptive pain suggest that different mechanisms are operating, possibly at a thalamocortical level. Implications for treatment

  4. Oxygen-reducing catalyst layer

    DOEpatents

    O'Brien, Dennis P [Maplewood, MN; Schmoeckel, Alison K [Stillwater, MN; Vernstrom, George D [Cottage Grove, MN; Atanasoski, Radoslav [Edina, MN; Wood, Thomas E [Stillwater, MN; Yang, Ruizhi [Halifax, CA; Easton, E Bradley [Halifax, CA; Dahn, Jeffrey R [Hubley, CA; O'Neill, David G [Lake Elmo, MN

    2011-03-22

    An oxygen-reducing catalyst layer, and a method of making the oxygen-reducing catalyst layer, where the oxygen-reducing catalyst layer includes a catalytic material film disposed on a substrate with the use of physical vapor deposition and thermal treatment. The catalytic material film includes a transition metal that is substantially free of platinum. At least one of the physical vapor deposition and the thermal treatment is performed in a processing environment comprising a nitrogen-containing gas.

  5. Reduced Gravity Zblan Optical Fiber

    NASA Technical Reports Server (NTRS)

    Tucker, Dennis S.; Workman, Gary L.; Smith, Guy A.

    2000-01-01

    Two optical fiber pullers have been designed for pulling ZBLAN optical fiber in reduced gravity. One fiber puller was designed, built and flown on board NASA's KC135 reduced gravity aircraft. A second fiber puller has been designed for use on board the International Space Station.

  6. Barefoot Running Reduces the Submaximal Oxygen Cost in Female Distance Runners.

    PubMed

    Berrones, Adam J; Kurti, Stephanie P; Kilsdonk, Korey M; Cortez, Delonyx J; Melo, Flavia F; Whitehurst, Michael

    2016-08-01

    Berrones, AJ, Kurti, SP, Kilsdonk, KM, Cortez, DJ, Melo, FF, and Whitehurst, M. Barefoot running reduces the submaximal oxygen cost in female distance runners. J Strength Cond Res 30(8): 2348-2353, 2016-Being a competitive distance runner is, in part, attributable to a high V[Combining Dot Above]O2max. However, running economy (RE) is a more robust indicator of distance running performance among endurance athletes of similar V[Combining Dot Above]O2max levels. The purpose of this study was to examine the influence of unshod (barefoot) vs. shod (wearing shoes) running on RE (expressed as ml·kg·min) during three 5-minute submaximal running trials representing 65, 75, and 85% of V[Combining Dot Above]O2max. Other physiologic and perceptual variables such as respiratory exchange ratio, lactate, heart rate, and ratings of perceived exertion were also chosen as dependent variables. We measured V[Combining Dot Above]O2max in 14 recreationally active trained distance female runners (age = 27.6 ± 1.6 years; height = 163.3 ± 1.7 cm; weight = 57.8 ± 1.9 kg) who were completely inexperienced with unshod running. After initial testing, each subject was randomized to either unshod or shod for days 2 and 3. We analyzed the data with a 2-way (condition by intensity) repeated-measures analysis of variance. Submaximal oxygen consumption was significantly reduced at 85% of V[Combining Dot Above]O2max (p = 0.018), indicating an improvement in RE, but not during the 65% or 75% trials (p > 0.05, both). No other dependent measure was different between unshod and shod conditions. Our results indicate that the immediate improvement to RE while barefoot occurs at a relatively high fraction of maximal oxygen consumption. For the recreational or competitive distance runner, training or competing while barefoot may be a useful strategy to improve endurance performance.

  7. Reducing crosstalk between stereoscopic views

    NASA Astrophysics Data System (ADS)

    Lipscomb, James S.; Wooten, Wayne L.

    1994-04-01

    Crosstalk between the left and right eyes consists of the one eye's image seen faintly by the other. Image processing can reduce this. The technique is effective, but there are costs of course, and some surprises.

  8. Reducing Cancer Patients' Painful Treatment

    NASA Video Gallery

    A NASA light technology originally developed to aid plant growth experiments in space has proved to reduce the painful side effects resulting from chemotherapy and radiation treatment in bone marro...

  9. Reduced Gravity Education Flight Program

    NASA Video Gallery

    NASA'€™s Reduced Gravity Education Flight Program gives students and educators the opportunity to design, build and fly an experiment in microgravity and get a look at what it takes to be a NASA en...

  10. ISS Update: Reduced Gravity Education

    NASA Video Gallery

    NASA Public Affairs Officer Dan Huot interviews Veronica Seyl, Acting Manager for Reduced Gravity Education. NASA works with students and educators to design experiments for flight testing aboard t...

  11. How to Reduce Solid Waste.

    ERIC Educational Resources Information Center

    Martins, George; Clapp, Leallyn B.

    1974-01-01

    Discusses the problem of solid waste disposal in the United States, suggests ways in which solid wastes might be reduced, and proposes a number of related topics for student debate in classes or in science clubs. (JR)

  12. Learning to REDUCE: A Reduced Electricity Consumption Prediction Ensemble

    SciTech Connect

    Aman, Saima; Chelmis, Charalampos; Prasanna, Viktor

    2016-02-12

    Utilities use Demand Response (DR) to balance supply and demand in the electric grid by involving customers in efforts to reduce electricity consumption during peak periods. To implement and adapt DR under dynamically changing conditions of the grid, reliable prediction of reduced consumption is critical. However, despite the wealth of research on electricity consumption prediction and DR being long in practice, the problem of reduced consumption prediction remains largely un-addressed. In this paper, we identify unique computational challenges associated with the prediction of reduced consumption and contrast this to that of normal consumption and DR baseline prediction.We propose a novel ensemble model that leverages different sequences of daily electricity consumption on DR event days as well as contextual attributes for reduced consumption prediction. We demonstrate the success of our model on a large, real-world, high resolution dataset from a university microgrid comprising of over 950 DR events across a diverse set of 32 buildings. Our model achieves an average error of 13.5%, an 8.8% improvement over the baseline. Our work is particularly relevant for buildings where electricity consumption is not tied to strict schedules. Our results and insights should prove useful to the researchers and practitioners working in the sustainable energy domain.

  13. The selective estrogen receptor modulator, bazedoxifene, reduces ischemic brain damage in male rat.

    PubMed

    Castelló-Ruiz, María; Torregrosa, Germán; Burguete, María C; Miranda, Francisco J; Centeno, José M; López-Morales, Mikahela A; Gasull, Teresa; Alborch, Enrique

    2014-07-11

    While the estrogen treatment of stroke is under debate, selective estrogen receptor modulators (SERMs) arise as a promising alternative. We hypothesize that bazedoxifene (acetate, BZA), a third generation SERM approved for the treatment of postmenopausal osteoporosis, reduces ischemic brain damage in a rat model of transient focal cerebral ischemia. For comparative purposes, the neuroprotective effect of 17β-estradiol (E2) has also been assessed. Male Wistar rats underwent 60min middle cerebral artery occlusion (intraluminal thread technique), and grouped according to treatment: vehicle-, E2- and BZA-treated rats. Optimal plasma concentrations of E2 (45.6±7.8pg/ml) and BZA (20.7±2.1ng/ml) were achieved 4h after onset of ischemia, and maintained until the end of the procedure (24h). Neurofunctional score and volume of the damaged brain regions were the main end points. At 24h after ischemia-reperfusion, neurofunctional examination of the animals did not show significant differences among the three experimental groups. By contrast, both E2- and BZA-treated groups showed significantly lower total infarct volumes, BZA acting mainly in the cortical region and E2 acting mainly at the subcortical level. Our results demonstrate that: (1) E2 at physiological plasma levels in female rats is neuroprotective in male rats when given at the acute stage of the ischemic challenge and (2) BZA at clinically relevant plasma levels mimics the neuroprotective action of E2 and could be, therefore, a candidate in stroke treatment.

  14. Determining Reduced Order Models for Optimal Stochastic Reduced Order Models

    SciTech Connect

    Bonney, Matthew S.; Brake, Matthew R.W.

    2015-08-01

    The use of parameterized reduced order models(PROMs) within the stochastic reduced order model (SROM) framework is a logical progression for both methods. In this report, five different parameterized reduced order models are selected and critiqued against the other models along with truth model for the example of the Brake-Reuss beam. The models are: a Taylor series using finite difference, a proper orthogonal decomposition of the the output, a Craig-Bampton representation of the model, a method that uses Hyper-Dual numbers to determine the sensitivities, and a Meta-Model method that uses the Hyper-Dual results and constructs a polynomial curve to better represent the output data. The methods are compared against a parameter sweep and a distribution propagation where the first four statistical moments are used as a comparison. Each method produces very accurate results with the Craig-Bampton reduction having the least accurate results. The models are also compared based on time requirements for the evaluation of each model where the Meta- Model requires the least amount of time for computation by a significant amount. Each of the five models provided accurate results in a reasonable time frame. The determination of which model to use is dependent on the availability of the high-fidelity model and how many evaluations can be performed. Analysis of the output distribution is examined by using a large Monte-Carlo simulation along with a reduced simulation using Latin Hypercube and the stochastic reduced order model sampling technique. Both techniques produced accurate results. The stochastic reduced order modeling technique produced less error when compared to an exhaustive sampling for the majority of methods.

  15. Strategies to Reduce Indoor Tanning

    PubMed Central

    Holman, Dawn M.; Fox, Kathleen A.; Glenn, Jeffrey D.; Guy, Gery P.; Watson, Meg; Baker, Katie; Cokkinides, Vilma; Gottlieb, Mark; Lazovich, DeAnn; Perna, Frank M.; Sampson, Blake P.; Seidenberg, Andrew B.; Sinclair, Craig; Geller, Alan C.

    2015-01-01

    Exposure to ultraviolet radiation from indoor tanning device use is associated with an increased risk of skin cancer, including risk of malignant melanoma, and is an urgent public health problem. By reducing indoor tanning, future cases of skin cancer could be prevented, along with the associated morbidity, mortality, and healthcare costs. On August 20, 2012, the CDC hosted a meeting to discuss the current body of evidence on strategies to reduce indoor tanning as well as research gaps. Using the Action Model to Achieve Healthy People 2020 Overarching Goals as a framework, the current paper provides highlights on the topics that were discussed, including (1) the state of the evidence on strategies to reduce indoor tanning; (2) the tools necessary to effectively assess, monitor, and evaluate the short- and long-term impact of interventions designed to reduce indoor tanning; and (3) strategies to align efforts at the national, state, and local levels through transdisciplinary collaboration and coordination across multiple sectors. Although many challenges and barriers exist, a coordinated, multilevel, transdisciplinary approach has the potential to reduce indoor tanning and prevent future cases of skin cancer. PMID:23683986

  16. Sleep can reduce proactive interference.

    PubMed

    Abel, Magdalena; Bäuml, Karl-Heinz T

    2014-01-01

    Sleep has repeatedly been connected to processes of memory consolidation. While extensive research indeed documents beneficial effects of sleep on memory, little is yet known about the role of sleep for interference effects in episodic memory. Although two prior studies reported sleep to reduce retroactive interference, no sleep effect has previously been found for proactive interference. Here we applied a study format differing from that employed by the prior studies to induce a high degree of proactive interference, and asked participants to encode a single list or two interfering lists of paired associates via pure study cycles. Testing occurred after 12 hours of diurnal wakefulness or nocturnal sleep. Consistent with the prior work, we found sleep in comparison to wake did not affect memory for the single list, but reduced retroactive interference. In addition we found sleep reduced proactive interference, and reduced retroactive and proactive interference to the same extent. The finding is consistent with the view that arising benefits of sleep are caused by the reactivation of memory contents during sleep, which has been suggested to strengthen and stabilise memories. Such stabilisation may make memories less susceptible to competition from interfering memories at test and thus reduce interference effects.

  17. Reduce air, reduce compliance cost new patented spray booth technology

    SciTech Connect

    McGinnis, F.

    1997-12-31

    A New Paint Spray Booth System that dramatically reduces air volumes normally required for capturing and controlling paint overspray that contains either Volatile Organic Compounds (VOC) or Hazardous Air Pollutants (HAP), or both. In turn, a substantial reduction in capital equipment expenditures for air abatement systems and air make-up heaters as well as related annual operating expenses is realized.

  18. Power and reduced temporal discounting.

    PubMed

    Joshi, Priyanka D; Fast, Nathanael J

    2013-04-01

    Decision makers generally feel disconnected from their future selves, an experience that leads them to prefer smaller immediate gains to larger future gains. This pervasive tendency is known as temporal discounting, and researchers across disciplines are interested in understanding how to overcome it. Following recent advances in the power literature, we suggest that the experience of power enhances one's connection with the future self, which in turn results in reduced temporal discounting. In Study 1, we found that participants assigned to high-power roles were less likely than participants assigned to low-power roles to display temporal discounting. In Studies 2 and 3, priming power reduced temporal discounting in monetary and nonmonetary tasks, and, further, connection with the future self mediated the relation between power and reduced discounting. In Study 4, experiencing a general sense of power in the workplace predicted actual lifetime savings. These results have important implications for future research.

  19. Microbial methods of reducing technetium

    DOEpatents

    Wildung, Raymond E [Richland, WA; Garland, Thomas R [Greybull, WY; Gorby, Yuri A [Richland, WA; Hess, Nancy J [Benton City, WA; Li, Shu-Mei W [Richland, WA; Plymale, Andrew E [Richland, WA

    2001-01-01

    The present invention is directed toward a method for microbial reduction of a technetium compound to form other compounds of value in medical imaging. The technetium compound is combined in a mixture with non-growing microbial cells which contain a technetium-reducing enzyme system, a stabilizing agent and an electron donor in a saline solution under anaerobic conditions. The mixture is substantially free of an inorganic technetium reducing agent and its reduction products. The resulting product is Tc of lower oxidation states, the form of which can be partially controlled by the stabilizing agent. It has been discovered that the microorganisms Shewanella alga, strain Bry and Shewanelia putrifacians, strain CN-32 contain the necessary enzyme systems for technetium reduction and can form both mono nuclear and polynuclear reduced Tc species depending on the stabilizing agent.

  20. Contrasting reduced overshadowing and blocking.

    PubMed

    Wheeler, Daniel S; Miller, Ralph R

    2007-07-01

    Preexposure of a cue without an outcome (X-) prior to compound pairings with the outcome (XZ-->O) can reduce overshadowing of a target cue (Z). Moreover, pairing a cue with an outcome (X-->O) before compound training can enhance its ability to compete with another cue (i.e., blocking). Four experiments were conducted in a conditioned bar-press suppression preparation with rats to determine whether spacing of the X- or X-->O trials would differentially affect reduced overshadowing and blocking. Experiment 1a showed that reduced overshadowing was larger with massed trials than with spaced trials. Experiment 1b found that blocking was larger with spaced trials than with massed trials. Experiments 2a and 2b indicated that these effects of trial spacing were both mediated by the associative status of the context at test. The results are interpreted in the framework of contemporary learning theories.

  1. Six ways to reduce inventory.

    PubMed

    Lunn, T

    1996-05-01

    The purpose of this presentation is to help you reduce the inventory in your operation. We will accomplish that task by discussing six specific methods that companies have used successfully to reduce their inventory. One common attribute of these successes is that they also build teamwork among the people. Every business operation today is concerned with methods to improve customer service. The real trick is to accomplish that task without increasing inventory. We are all concerned with improving our skills at keeping inventory low.

  2. Flexure Bearing Reduces Startup Friction

    NASA Technical Reports Server (NTRS)

    Clingman, W. Dean

    1991-01-01

    Design concept for ball bearing incorporates small pieces of shim stock, wire spokes like those in bicycle wheels, or other flexing elements to reduce both stiction and friction slope. In flexure bearing, flexing elements placed between outer race of ball bearing and outer ring. Elements flex when ball bearings encounter small frictional-torque "bumps" or even larger ones when bearing balls encounter buildups of grease on inner or outer race. Flexure of elements reduce high friction slopes of "bumps", helping to keep torque between outer ring and inner race low and more nearly constant. Concept intended for bearings in gimbals on laser and/or antenna mirrors.

  3. Reducing Life-Cycle Costs.

    ERIC Educational Resources Information Center

    Roodvoets, David L.

    2003-01-01

    Presents factors to consider when determining roofing life-cycle costs, explaining that costs do not tell the whole story; discussing components that should go into the decision (cost, maintenance, energy use, and environmental costs); and concluding that important elements in reducing life-cycle costs include energy savings through increased…

  4. METHOD OF REDUCING PLUTONIUM COMPOUNDS

    DOEpatents

    Johns, I.B.

    1958-06-01

    A method is described for reducing plutonium compounds in aqueous solution from a higher to a lower valence state. This reduction of valence is achieved by treating the aqueous solution of higher valence plutonium compounds with hydrogen in contact with an activated platinum catalyst.

  5. Reduced False Memory after Sleep

    ERIC Educational Resources Information Center

    Fenn, Kimberly M.; Gallo, David A.; Margoliash, Daniel; Roediger, Henry L., III; Nusbaum, Howard C.

    2009-01-01

    Several studies have shown that sleep contributes to the successful maintenance of previously encoded information. This research has focused exclusively on memory for studied events, as opposed to false memories. Here we report three experiments showing that sleep reduces false memories in the Deese-Roediger-McDermott (DRM) memory illusion. False…

  6. Reducing Crime by Eliminating Cash.

    ERIC Educational Resources Information Center

    Warwick, David R.

    Ending the use of cash in the United States can provide substantial social and economic gain while requiring only modest levels of investment. One primary benefit is the reduction of cash-related crimes. Because most street crime is committed to obtain cash or uses cash as a transaction medium, elimination of cash will dramatically reduce crime.…

  7. Reduce Waste for Greener Holidays

    EPA Pesticide Factsheets

    DALLAS - (Dec. 15, 2015) Friends, family, parties, and travel are what make the holiday season great. You can make it even better by reducing waste as often as possible during your celebrations. The U.S. Environmental Protection Agency (EPA) wants t

  8. Reference Works in Reduced Size

    ERIC Educational Resources Information Center

    Hennessey, David

    1977-01-01

    Lower cost and less shelf space requirements have made major reference works in miniaturized print editions attractive to small libraries. The major disadvantage is the necessity of a magnifying glass for reading entries. A bibliography of reduced-size editions is included. (JAB)

  9. Reducing cement's CO2 footprint

    USGS Publications Warehouse

    van Oss, Hendrik G.

    2011-01-01

    The manufacturing process for Portland cement causes high levels of greenhouse gas emissions. However, environmental impacts can be reduced by using more energy-efficient kilns and replacing fossil energy with alternative fuels. Although carbon capture and new cements with less CO2 emission are still in the experimental phase, all these innovations can help develop a cleaner cement industry.

  10. Hindlimb suspension reduces muscle regeneration

    NASA Technical Reports Server (NTRS)

    Mozdziak, P. E.; Truong, Q.; Macius, A.; Schultz, E.

    1998-01-01

    Exposure of juvenile skeletal muscle to a weightless environment reduces growth and satellite cell mitotic activity. However, the effect of a weightless environment on the satellite cell population during muscle repair remains unknown. Muscle injury was induced in rat soleus muscles using the myotoxic snake venom, notexin. Rats were placed into hindlimb-suspended or weightbearing groups for 10 days following injury. Cellular proliferation during regeneration was evaluated using 5-bromo-2'-deoxyuridine (BrdU) immunohistochemistry and image analysis. Hindlimb suspension reduced (P < 0.05) regenerated muscle mass, regenerated myofiber diameter, uninjured muscle mass, and uninjured myofiber diameter compared to weightbearing rats. Hindlimb suspension reduced (P < 0.05) BrdU labeling in uninjured soleus muscles compared to weight-bearing muscles. However, hindlimb suspension did not abolish muscle regeneration because myofibers formed in the injured soleus muscles of hindlimb-suspended rats, and BrdU labeling was equivalent (P > 0.10) on myofiber segments isolated from the soleus muscles of hindlimb-suspended and weightbearing rats following injury. Thus, hindlimb suspension (weightlessness) does not suppress satellite cell mitotic activity in regenerating muscles before myofiber formation, but reduces growth of the newly formed myofibers.

  11. Reducing Poverty through Preschool Interventions

    ERIC Educational Resources Information Center

    Duncan, Greg J.; Ludwig, Jens; Magnuson, Katherine A.

    2007-01-01

    Greg Duncan, Jens Ludwig, and Katherine Magnuson explain how providing high-quality care to disadvantaged preschool children can help reduce poverty. In early childhood, they note, children's cognitive and socioemotional skills develop rapidly and are sensitive to "inputs" from parents, home learning environments, child care settings, and the…

  12. Do Rewards Reduce Student Motivation?

    ERIC Educational Resources Information Center

    Malouf, David

    1983-01-01

    The reduced continuing motivation effect is examined with regard to research, theory, and implications for practice. The description of research focuses primarily on studies conducted with preschool-aged or school-aged subjects. Explanations based on self-perception or attributional theory and learning theory are examined. (Author/PN)

  13. Reduced-vibration tube array

    DOEpatents

    Bruck, Gerald J.; Bartolomeo, Daniel R.

    2004-07-20

    A reduced-vibration tube array is disclosed. The array includes a plurality of tubes in a fixed arrangement and a plurality of damping members positioned within the tubes. The damping members include contoured interface regions characterized by bracing points that selectively contact the inner surface of an associated tube. Each interface region is sized and shaped in accordance with the associated tube, so that the damping member bracing points are spaced apart a vibration-reducing distance from the associated tube inner surfaces at equilibrium. During operation, mechanical interaction between the bracing points and the tube inner surfaces reduces vibration by a damage-reducing degree. In one embodiment, the interface regions are serpentine shaped. In another embodiment, the interface regions are helical in shape. The interface regions may be simultaneously helical and serpentine in shape. The damping members may be fixed within the associated tubes, and damping member may be customized several interference regions having attributes chosen in accordance with desired flow characteristics and associated tube properties.

  14. Pressure Reducer for Coal Gasifiers

    NASA Technical Reports Server (NTRS)

    Kendall, James M., Sr.

    1983-01-01

    Quasi-porous-plug pressure reducer is designed for gases containing abrasive particles. Gas used to generate high pressure steam to drive electric power generators. In giving up heat to steam, gas drops in temperature. Device used for coal gasification plants.

  15. Distinguishing iron-reducing from sulfate-reducing conditions

    USGS Publications Warehouse

    Chapelle, F.H.; Bradley, P.M.; Thomas, M.A.; McMahon, P.B.

    2009-01-01

    Ground water systems dominated by iron- or sulfate-reducing conditions may be distinguished by observing concentrations of dissolved iron (Fe2+) and sulfide (sum of H2S, HS-, and S= species and denoted here as "H2S"). This approach is based on the observation that concentrations of Fe2+ and H2S in ground water systems tend to be inversely related according to a hyperbolic function. That is, when Fe2+ concentrations are high, H2S concentrations tend to be low and vice versa. This relation partly reflects the rapid reaction kinetics of Fe2+ with H2S to produce relatively insoluble ferrous sulfides (FeS). This relation also reflects competition for organic substrates between the iron- and the sulfate-reducing microorganisms that catalyze the production of Fe2+ and H 2S. These solubility and microbial constraints operate in tandem, resulting in the observed hyperbolic relation between Fe2+ and H 2S concentrations. Concentrations of redox indicators, including dissolved hydrogen (H2) measured in a shallow aquifer in Hanahan, South Carolina, suggest that if the Fe2+/H2S mass ratio (units of mg/L) exceeded 10, the screened interval being tapped was consistently iron reducing (H2 ???0.2 to 0.8 nM). Conversely, if the Fe 2+/H2S ratio was less than 0.30, consistent sulfate-reducing (H2 ???1 to 5 nM) conditions were observed over time. Concomitantly high Fe2+ and H2S concentrations were associated with H2 concentrations that varied between 0.2 and 5.0 nM over time, suggesting mixing of water from adjacent iron- and sulfate-reducing zones or concomitant iron and sulfate reduction under nonelectron donor-limited conditions. These observations suggest that Fe2+/H2S mass ratios may provide useful information concerning the occurrence and distribution of iron and sulfate reduction in ground water systems. ?? 2009 National Ground Water Association.

  16. Structural reducibility of multilayer networks

    NASA Astrophysics Data System (ADS)

    de Domenico, Manlio; Nicosia, Vincenzo; Arenas, Alexandre; Latora, Vito

    2015-04-01

    Many complex systems can be represented as networks consisting of distinct types of interactions, which can be categorized as links belonging to different layers. For example, a good description of the full protein-protein interactome requires, for some organisms, up to seven distinct network layers, accounting for different genetic and physical interactions, each containing thousands of protein-protein relationships. A fundamental open question is then how many layers are indeed necessary to accurately represent the structure of a multilayered complex system. Here we introduce a method based on quantum theory to reduce the number of layers to a minimum while maximizing the distinguishability between the multilayer network and the corresponding aggregated graph. We validate our approach on synthetic benchmarks and we show that the number of informative layers in some real multilayer networks of protein-genetic interactions, social, economical and transportation systems can be reduced by up to 75%.

  17. Alcohol reduces aversion to ambiguity.

    PubMed

    Tyszka, Tadeusz; Macko, Anna; Stańczak, Maciej

    2014-01-01

    Several years ago, Cohen et al. (1958) demonstrated that under the influence of alcohol drivers became more risk prone, although their risk perception remained unchanged. Research shows that ambiguity aversion is to some extent positively correlated with risk aversion, though not very highly (Camerer and Weber, 1992). The question addressed by the present research is whether alcohol reduces ambiguity aversion. Our research was conducted in a natural setting (a restaurant bar), where customers with differing levels of alcohol intoxication were offered a choice between a risky and an ambiguous lottery. We found that alcohol reduced ambiguity aversion and that the effect occurred in men but not women. We interpret these findings in terms of the risk-as-value hypothesis, according to which, people in Western culture tend to value risk, and suggest that alcohol consumption triggers adherence to socially and culturally valued patterns of conduct different for men and women.

  18. Contrails reduce daily temperature range.

    PubMed

    Travis, David J; Carleton, Andrew M; Lauritsen, Ryan G

    2002-08-08

    The potential of condensation trails (contrails) from jet aircraft to affect regional-scale surface temperatures has been debated for years, but was difficult to verify until an opportunity arose as a result of the three-day grounding of all commercial aircraft in the United States in the aftermath of the terrorist attacks on 11 September 2001. Here we show that there was an anomalous increase in the average diurnal temperature range (that is, the difference between the daytime maximum and night-time minimum temperatures) for the period 11-14 September 2001. Because persisting contrails can reduce the transfer of both incoming solar and outgoing infrared radiation and so reduce the daily temperature range, we attribute at least a portion of this anomaly to the absence of contrails over this period.

  19. Reducing carbon dioxide to products

    SciTech Connect

    Cole, Emily Barton; Sivasankar, Narayanappa; Parajuli, Rishi; Keets, Kate A

    2014-09-30

    A method reducing carbon dioxide to one or more products may include steps (A) to (C). Step (A) may bubble said carbon dioxide into a solution of an electrolyte and a catalyst in a divided electrochemical cell. The divided electrochemical cell may include an anode in a first cell compartment and a cathode in a second cell compartment. The cathode may reduce said carbon dioxide into said products. Step (B) may adjust one or more of (a) a cathode material, (b) a surface morphology of said cathode, (c) said electrolyte, (d) a manner in which said carbon dioxide is bubbled, (e), a pH level of said solution, and (f) an electrical potential of said divided electrochemical cell, to vary at least one of (i) which of said products is produced and (ii) a faradaic yield of said products. Step (C) may separate said products from said solution.

  20. Mindfulness reduces the correspondence bias.

    PubMed

    Hopthrow, Tim; Hooper, Nic; Mahmood, Lynsey; Meier, Brian P; Weger, Ulrich

    2017-03-01

    The correspondence bias (CB) refers to the idea that people sometimes give undue weight to dispositional rather than situational factors when explaining behaviours and attitudes. Three experiments examined whether mindfulness, a non-judgmental focus on the present moment, could reduce the CB. Participants engaged in a brief mindfulness exercise (the raisin task), a control task, or an attention to detail task before completing a typical CB measure involving an attitude-attribution paradigm. The results indicated that participants in the mindfulness condition experienced a significant reduction in the CB compared to participants in the control or attention to detail conditions. These results suggest that mindfulness training can play a unique role in reducing social biases related to person perception.

  1. Alcohol reduces aversion to ambiguity

    PubMed Central

    Tyszka, Tadeusz; Macko, Anna; Stańczak, Maciej

    2015-01-01

    Several years ago, Cohen et al. (1958) demonstrated that under the influence of alcohol drivers became more risk prone, although their risk perception remained unchanged. Research shows that ambiguity aversion is to some extent positively correlated with risk aversion, though not very highly (Camerer and Weber, 1992). The question addressed by the present research is whether alcohol reduces ambiguity aversion. Our research was conducted in a natural setting (a restaurant bar), where customers with differing levels of alcohol intoxication were offered a choice between a risky and an ambiguous lottery. We found that alcohol reduced ambiguity aversion and that the effect occurred in men but not women. We interpret these findings in terms of the risk-as-value hypothesis, according to which, people in Western culture tend to value risk, and suggest that alcohol consumption triggers adherence to socially and culturally valued patterns of conduct different for men and women. PMID:25642202

  2. Correlated Electrons in Reduced Dimensions

    SciTech Connect

    Bonesteel, Nicholas E

    2015-01-31

    This report summarizes the work accomplished under the support of US DOE grant # DE-FG02-97ER45639, "Correlated Electrons in Reduced Dimensions." The underlying hypothesis of the research supported by this grant has been that studying the unique behavior of correlated electrons in reduced dimensions can lead to new ways of understanding how matter can order and how it can potentially be used. The systems under study have included i) fractional quantum Hall matter, which is realized when electrons are confined to two-dimensions and placed in a strong magnetic field at low temperature, ii) one-dimensional chains of spins and exotic quasiparticle excitations of topologically ordered matter, and iii) electrons confined in effectively ``zero-dimensional" semiconductor quantum dots.

  3. Ferroelectric capacitor with reduced imprint

    DOEpatents

    Evans, Jr., Joseph T.; Warren, William L.; Tuttle, Bruce A.; Dimos, Duane B.; Pike, Gordon E.

    1997-01-01

    An improved ferroelectric capacitor exhibiting reduced imprint effects in comparison to prior art capacitors. A capacitor according to the present invention includes top and bottom electrodes and a ferroelectric layer sandwiched between the top and bottom electrodes, the ferroelectric layer comprising a perovskite structure of the chemical composition ABO.sub.3 wherein the B-site comprises first and second elements and a dopant element that has an oxidation state greater than +4. The concentration of the dopant is sufficient to reduce shifts in the coercive voltage of the capacitor with time. In the preferred embodiment of the present invention, the ferroelectric element comprises Pb in the A-site, and the first and second elements are Zr and Ti, respectively. The preferred dopant is chosen from the group consisting of Niobium, Tantalum, and Tungsten. In the preferred embodiment of the present invention, the dopant occupies between 1 and 8% of the B-sites.

  4. Tandem motors reduce well costs

    SciTech Connect

    Hooper, M.; Daigle, C.; Crowe, R.

    1995-10-01

    The new generation of tandem mud motors that recently appeared on the drilling scene is significantly affecting drilling efficiency worldwide. These motors provide drillers with increased horsepower at the bit, higher torque, and faster rates of penetration (ROP). With advanced engineering and more durable materials, motor life is being extended, thereby increasing the time between bit trips and reducing drilling costs. This article reviews the performance, design, and operation of these motors.

  5. MapReduce SVM Game

    SciTech Connect

    Vineyard, Craig M.; Verzi, Stephen J.; James, Conrad D.; Aimone, James B.; Heileman, Gregory L.

    2015-08-10

    Despite technological advances making computing devices faster, smaller, and more prevalent in today's age, data generation and collection has outpaced data processing capabilities. Simply having more compute platforms does not provide a means of addressing challenging problems in the big data era. Rather, alternative processing approaches are needed and the application of machine learning to big data is hugely important. The MapReduce programming paradigm is an alternative to conventional supercomputing approaches, and requires less stringent data passing constrained problem decompositions. Rather, MapReduce relies upon defining a means of partitioning the desired problem so that subsets may be computed independently and recom- bined to yield the net desired result. However, not all machine learning algorithms are amenable to such an approach. Game-theoretic algorithms are often innately distributed, consisting of local interactions between players without requiring a central authority and are iterative by nature rather than requiring extensive retraining. Effectively, a game-theoretic approach to machine learning is well suited for the MapReduce paradigm and provides a novel, alternative new perspective to addressing the big data problem. In this paper we present a variant of our Support Vector Machine (SVM) Game classifier which may be used in a distributed manner, and show an illustrative example of applying this algorithm.

  6. MapReduce SVM Game

    DOE PAGES

    Vineyard, Craig M.; Verzi, Stephen J.; James, Conrad D.; ...

    2015-08-10

    Despite technological advances making computing devices faster, smaller, and more prevalent in today's age, data generation and collection has outpaced data processing capabilities. Simply having more compute platforms does not provide a means of addressing challenging problems in the big data era. Rather, alternative processing approaches are needed and the application of machine learning to big data is hugely important. The MapReduce programming paradigm is an alternative to conventional supercomputing approaches, and requires less stringent data passing constrained problem decompositions. Rather, MapReduce relies upon defining a means of partitioning the desired problem so that subsets may be computed independently andmore » recom- bined to yield the net desired result. However, not all machine learning algorithms are amenable to such an approach. Game-theoretic algorithms are often innately distributed, consisting of local interactions between players without requiring a central authority and are iterative by nature rather than requiring extensive retraining. Effectively, a game-theoretic approach to machine learning is well suited for the MapReduce paradigm and provides a novel, alternative new perspective to addressing the big data problem. In this paper we present a variant of our Support Vector Machine (SVM) Game classifier which may be used in a distributed manner, and show an illustrative example of applying this algorithm.« less

  7. Interventions to Reduce Sedentary Behavior

    PubMed Central

    Manini, Todd M.; Carr, Lucas J.; King, Abby C.; Marshall, Simon; Robinson, Thomas N.; Rejeski, W. Jack

    2014-01-01

    Purpose This paper reports on presentations and discussion from the working group on “Influences on Sedentary Behavior & Interventions” as part of the Sedentary Behavior: Identifying Research Priorities Workshop. Methods Interventions were discussed in the context of targeting sedentary behavior (SB) as a concept distinct from physical activity (PA). It was recommended that interventions targeting SB should consider a life course perspective, a position predicated on the assumption that SB is age and life stage dependent. Additionally, targeting environments where individuals have high exposure to SB— such as workplace sitting— could benefit from new technology (e.g., computer-based prompting to stand or move), environmental changes (e.g., active workstations), policies targeting reduced sedentary time (e.g., allowing employees regular desk breaks), or by changing norms surrounding prolonged sitting (e.g., standing meetings). Results & Conclusions There are limited data about the minimal amount of SB change required to produce meaningful health benefits. In addition to developing relevant scientific and public health definitions of SB, it is important to further delineate the scope of health and quality of life outcomes associated with reduced SB across the life course, and clarify what behavioral alternatives to SB can be used to optimize health gains. SB interventions will benefit from having more clarity about the potential physiological and behavioral synergies with current PA recommendations, developing multi-level interventions aimed at reducing SB across all life phases and contexts, harnessing relevant and effective strategies to extend the reach of interventions to all sectors of society, as well as applying state-of-the-science adaptive designs and methods to accelerate advances in the science of sedentary behavior interventions. PMID:25222818

  8. Empowerment to reduce health disparities.

    PubMed

    Wallerstein, Nina

    2002-01-01

    This article articulates the theoretical construct of empowerment and its importance for health-enhancing strategies to reduce health disparities. Powerlessness is explored as a risk factor in the context of social determinants, such as poverty, discrimination, workplace hazards, and income inequities. Empowerment is presented and compared with social capital and community capacity as strategies to strengthen social protective factors. A case study of a youth empowerment and policy project in New Mexico illustrates the usefulness of empowerment strategies in both targeting social determinants, such as public policies which are detrimental to youth, and improving community capacities of youth to be advocates for social change. Challenges for future practice and research are articulated.

  9. Reducing rattlesnake-human conflicts

    USGS Publications Warehouse

    Nowak, Erika M.

    2006-01-01

    Arizona is home to 11 species of rattlesnakes. As rapidly growing Arizona communities move into formerly undeveloped landscapes, encounters between people and rattlesnakes increase. As a result, the management of nuisance snakes, or snakes found in areas where people do not want them, is increasingly important. Since 1994, the U.S. Geological Survey (USGS) has conducted research on the behavior and ecology of nuisance rattlesnake in Arizona national park units. A decade of research provides important insights into rattlesnake behavior that can be used by national parks and communities to reduce rattlesnake-human conflicts.

  10. Reduced Vlasov-Maxwell simulations

    NASA Astrophysics Data System (ADS)

    Helluy, Philippe; Navoret, Laurent; Pham, Nhung; Crestetto, Anaïs

    2014-10-01

    In this paper we review two different numerical methods for Vlasov-Maxwell simulations. The first method is based on a coupling between a Discontinuous Galerkin (DG) Maxwell solver and a Particle-In-Cell (PIC) Vlasov solver. The second method only uses a DG approach for the Vlasov and Maxwell equations. The Vlasov equation is first reduced to a space-only hyperbolic system thanks to the finite-element method. The two numerical methods are implemented using OpenCL in order to achieve high performance on recent Graphic Processing Units (GPU).

  11. The matricellular protein cysteine-rich protein 61 (CCN1/Cyr61) enhances physiological adaptation of retinal vessels and reduces pathological neovascularization associated with ischemic retinopathy.

    PubMed

    Hasan, Adeel; Pokeza, Nataliya; Shaw, Lynn; Lee, Hyun-Seung; Lazzaro, Douglas; Chintala, Hemabindu; Rosenbaum, Daniel; Grant, Maria B; Chaqour, Brahim

    2011-03-18

    Retinal vascular damages are the cardinal hallmarks of retinopathy of prematurity (ROP), a leading cause of vision impairment and blindness in childhood. Both angiogenesis and vasculogenesis are disrupted in the hyperoxia-induced vaso-obliteration phase, and recapitulated, although aberrantly, in the subsequent ischemia-induced neovessel formation phase of ROP. Yet, whereas the histopathological features of ROP are well characterized, many key modulators with a therapeutic potential remain unknown. The CCN1 protein also known as cysteine-rich protein 61 (Cyr61) is a dynamically expressed, matricellular protein required for proper angiogenesis and vasculogenesis during development. The expression of CCN1 becomes abnormally reduced during the hyperoxic and ischemic phases of ROP modeled in the mouse eye with oxygen-induced retinopathy (OIR). Lentivirus-mediated re-expression of CCN1 enhanced physiological adaptation of the retinal vasculature to hyperoxia and reduced pathological angiogenesis following ischemia. Remarkably, injection into the vitreous of OIR mice of hematopoietic stem cells (HSCs) engineered to express CCN1 harnessed ischemia-induced neovessel outgrowth without adversely affecting the physiological adaptation of retinal vessels to hyperoxia. In vitro exposure of HSCs to recombinant CCN1 induced integrin-dependent cell adhesion, migration, and expression of specific endothelial cell markers as well as many components of the Wnt signaling pathway including Wnt ligands, their receptors, inhibitors, and downstream targets. CCN1-induced Wnt signaling mediated, at least in part, adhesion and endothelial differentiation of cultured HSCs, and inhibition of Wnt signaling interfered with normalization of the retinal vasculature induced by CCN1-primed HSCs in OIR mice. These newly identified functions of CCN1 suggest its possible therapeutic utility in ischemic retinopathy.

  12. Reducing Misanthropic Memory Through Self-Awareness: Reducing Bias.

    PubMed

    Davis, Mark D

    2015-01-01

    Two experiments investigated the influence of self-awareness on misanthropic recall. Misanthropic recall is the tendency to recall more negative behaviors dispositionally attributed and positive behaviors situationally attributed than negative behaviors situationally attributed and positive behaviors dispositionally attributed. It was hypothesized that when one is self-aware, more systematic information processing would occur, thereby reducing misanthropic memory and influencing attitudinal judgments. The first experiment used a mirror and the second experiment used a live video to induce self-awareness. Participants were asked to form an impression of a group. The results of both experiments replicated the previously found pattern of misanthropic memory for non-self-aware participants (Ybarra & Stephan, 1996), and revealed less misanthropic recall bias in self-aware participants.

  13. Reduced prefrontal connectivity in psychopathy.

    PubMed

    Motzkin, Julian C; Newman, Joseph P; Kiehl, Kent A; Koenigs, Michael

    2011-11-30

    Linking psychopathy to a specific brain abnormality could have significant clinical, legal, and scientific implications. Theories on the neurobiological basis of the disorder typically propose dysfunction in a circuit involving ventromedial prefrontal cortex (vmPFC). However, to date there is limited brain imaging data to directly test whether psychopathy may indeed be associated with any structural or functional abnormality within this brain area. In this study, we employ two complementary imaging techniques to assess the structural and functional connectivity of vmPFC in psychopathic and non-psychopathic criminals. Using diffusion tensor imaging, we show that psychopathy is associated with reduced structural integrity in the right uncinate fasciculus, the primary white matter connection between vmPFC and anterior temporal lobe. Using functional magnetic resonance imaging, we show that psychopathy is associated with reduced functional connectivity between vmPFC and amygdala as well as between vmPFC and medial parietal cortex. Together, these data converge to implicate diminished vmPFC connectivity as a characteristic neurobiological feature of psychopathy.

  14. FIREhose: Reducing Data from FIRE

    NASA Astrophysics Data System (ADS)

    Fica, Haley Diane; Lambrides, Erini; Faherty, Jackie; Cruz, Kelle L.; BDNYC

    2016-01-01

    Brown dwarfs are stellar objects that do not have enough mass to ignite hydrogen fusion in their core. Their mass is between 0.08 solar masses and the mass of our sun. Brown dwarfs are very bright in the near-infrared wavelength band (0.8- 2.5 microns). We reduced data from the Folded-port InfraRed Echellette (FIRE) instrument on the Magellan Telescope at the Las Campanas Observatory. FIRE is a medium-resolution echelle spectrometer, whose data reduction results in a spectrum of a star. When reducing FIRE data, it is important to account for inconsistencies in the data, such as bad pixels, cosmic rays, and the effects of our atmosphere. Using the FIREhose pipeline, these inconsistencies can be accounted for and corrected using a A0 telluric with a known spectrum. After telluric correcting, the data reduction results in a primed spectrum for an object, which can then be used to determine an object's physical properties, such as atmospheric composition, radial velocity, effective temperature and surface gravity.

  15. Reduced discretization error in HZETRN

    SciTech Connect

    Slaba, Tony C.; Blattnig, Steve R.; Tweed, John

    2013-02-01

    The deterministic particle transport code HZETRN is an efficient analysis tool for studying the effects of space radiation on humans, electronics, and shielding materials. In a previous work, numerical methods in the code were reviewed, and new methods were developed that further improved efficiency and reduced overall discretization error. It was also shown that the remaining discretization error could be attributed to low energy light ions (A < 4) with residual ranges smaller than the physical step-size taken by the code. Accurately resolving the spectrum of low energy light particles is important in assessing risk associated with astronaut radiation exposure. In this work, modifications to the light particle transport formalism are presented that accurately resolve the spectrum of low energy light ion target fragments. The modified formalism is shown to significantly reduce overall discretization error and allows a physical approximation to be removed. For typical step-sizes and energy grids used in HZETRN, discretization errors for the revised light particle transport algorithms are shown to be less than 4% for aluminum and water shielding thicknesses as large as 100 g/cm{sup 2} exposed to both solar particle event and galactic cosmic ray environments.

  16. Interventions to reduce school bullying.

    PubMed

    Smith, Peter K; Ananiadou, Katerina; Cowie, Helen

    2003-10-01

    In the last 2 decades, school bullying has become a topic of public concern and research around the world. This has led to action to reduce the problem. We review interventions targeted at the school level (for example, whole school policy, classroom climate, peer support, school tribunal, and playground improvement), at the class level (for example, curriculum work), and at the individual level (for example, working with specific pupils). Effectiveness of interventions has been sporadically assessed. We review several systematically evaluated, large-scale, school-based intervention programs. Their effectiveness has varied, and we consider reasons for this. We suggest ways to improve the evaluation and comparability of studies, as well as the effectiveness of future interventions.

  17. Moral Violations Reduce Oral Consumption

    PubMed Central

    Chan, Cindy; Van Boven, Leaf; Andrade, Eduardo B.; Ariely, Dan

    2014-01-01

    Consumers frequently encounter moral violations in everyday life. They watch movies and television shows about crime and deception, hear news reports of corporate fraud and tax evasion, and hear gossip about cheaters and thieves. How does exposure to moral violations influence consumption? Because moral violations arouse disgust and because disgust is an evolutionarily important signal of contamination that should provoke a multi-modal response, we hypothesize that moral violations affect a key behavioral response to disgust: reduced oral consumption. In three experiments, compared with those in control conditions, people drank less water and chocolate milk while (a) watching a film portraying the moral violations of incest, (b) writing about moral violations of cheating or theft, and (c) listening to a report about fraud and manipulation. These findings imply that “moral disgust” influences consumption in ways similar to core disgust, and thus provide evidence for the associations between moral violations, emotions, and consumer behavior. PMID:25125931

  18. Moral Violations Reduce Oral Consumption.

    PubMed

    Chan, Cindy; Van Boven, Leaf; Andrade, Eduardo B; Ariely, Dan

    2014-07-01

    Consumers frequently encounter moral violations in everyday life. They watch movies and television shows about crime and deception, hear news reports of corporate fraud and tax evasion, and hear gossip about cheaters and thieves. How does exposure to moral violations influence consumption? Because moral violations arouse disgust and because disgust is an evolutionarily important signal of contamination that should provoke a multi-modal response, we hypothesize that moral violations affect a key behavioral response to disgust: reduced oral consumption. In three experiments, compared with those in control conditions, people drank less water and chocolate milk while (a) watching a film portraying the moral violations of incest, (b) writing about moral violations of cheating or theft, and (c) listening to a report about fraud and manipulation. These findings imply that "moral disgust" influences consumption in ways similar to core disgust, and thus provide evidence for the associations between moral violations, emotions, and consumer behavior.

  19. Reduced vibration motor winding arrangement

    DOEpatents

    Slavik, C.J.; Rhudy, R.G.; Bushman, R.E.

    1997-11-11

    An individual phase winding arrangement having a sixty electrical degree phase belt width for use with a three phase motor armature includes a delta connected phase winding portion and a wye connected phase winding portion. Both the delta and wye connected phase winding portions have a thirty electrical degree phase belt width. The delta and wye connected phase winding portions are each formed from a preselected number of individual coils each formed, in turn, from an unequal number of electrical conductor turns in the approximate ratio of {radical}3. The individual coils of the delta and wye connected phase winding portions may either be connected in series or parallel. This arrangement provides an armature winding for a three phase motor which retains the benefits of the widely known and utilized thirty degree phase belt concept, including improved mmf waveform and fundamental distribution factor, with consequent reduced vibrations and improved efficiency. 4 figs.

  20. Reduced vibration motor winding arrangement

    DOEpatents

    Slavik, Charles J.; Rhudy, Ralph G.; Bushman, Ralph E.

    1997-01-01

    An individual phase winding arrangement having a sixty electrical degree phase belt width for use with a three phase motor armature includes a delta connected phase winding portion and a wye connected phase winding portion. Both the delta and wye connected phase winding portions have a thirty electrical degree phase belt width. The delta and wye connected phase winding portions are each formed from a preselected number of individual coils each formed, in turn, from an unequal number of electrical conductor turns in the approximate ratio of .sqroot.3. The individual coils of the delta and wye connected phase winding portions may either be connected in series or parallel. This arrangement provides an armature winding for a three phase motor which retains the benefits of the widely known and utilized thirty degree phase belt concept, including improved mmf waveform and fundamental distribution factor, with consequent reduced vibrations and improved efficiency.

  1. The Influence of RGD-Bearing Hydrogels on the Re-expression of Contractile Vascular Smooth Muscle Cell Phenotype

    PubMed Central

    Beamish, Jeffrey A.; Fu, Alexander; Choi, Ae-jin; Haq, Nada; Kottke-Marchant, Kandice; Marchant, Roger E.

    2009-01-01

    This study reports on the ability of poly(ethylene glycol) diacrylate (PEGDA) hydrogel scaffolds with pendant integrin-binding GRGDSP peptides (RGD-gels) to support the re-differentiation of cultured vascular smooth muscle cells (SMCs) toward a contractile phenotype. Human coronary SMCs were seeded on RGD-gels, hydrogels with other extracellular matrix derived peptides, fibronectin (FN) and laminin (LN). Differentiation was induced on RGD-gels with low serum medium containing soluble heparin, and the differentiation status was monitored by mRNA expression, protein expression, and intracellular protein organization of the contractile smooth muscle markers, smooth muscle α-actin, calponin and SM-22α. RGD-gels supported a rapid induction (2.7- to 25-fold up-regulation) of SMC marker gene mRNA, with expression levels that were equivalent to FN and LN controls. Marker protein levels mirrored the changes in mRNA expression, with levels on RGD-gels indistinguishable from FN and LN controls. Furthermore, these markers co-localized in stress fibers within SMCs on RGD-gels suggesting the recapitulation of a contractile apparatus within the cells. These results indicate that SMCs cultured on RGD-bearing hydrogels can re-differentiate toward a contractile phenotype suggesting this material is an excellent candidate for further development as a bioactive scaffold that regulates SMC phenotype. PMID:19481795

  2. Reducing stillbirths: interventions during labour

    PubMed Central

    Darmstadt, Gary L; Yakoob, Mohammad Yawar; Haws, Rachel A; Menezes, Esme V; Soomro, Tanya; Bhutta, Zulfiqar A

    2009-01-01

    Background Approximately one million stillbirths occur annually during labour; most of these stillbirths occur in low and middle-income countries and are associated with absent, inadequate, or delayed obstetric care. The low proportion of intrapartum stillbirths in high-income countries suggests that intrapartum stillbirths are largely preventable with quality intrapartum care, including prompt recognition and management of intrapartum complications. The evidence for impact of intrapartum interventions on stillbirth and perinatal mortality outcomes has not yet been systematically examined. Methods We undertook a systematic review of the published literature, searching PubMed and the Cochrane Library, of trials and reviews (N = 230) that reported stillbirth or perinatal mortality outcomes for eight interventions delivered during labour. Where eligible randomised controlled trials had been published after the most recent Cochrane review on any given intervention, we incorporated these new trial findings into a new meta-analysis with the Cochrane included studies. Results We found a paucity of studies reporting statistically significant evidence of impact on perinatal mortality, especially on stillbirths. Available evidence suggests that operative delivery, especially Caesarean section, contributes to decreased stillbirth rates. Induction of labour rather than expectant management in post-term pregnancies showed strong evidence of impact, though there was not enough evidence to suggest superior safety for the fetus of any given drug or drugs for induction of labour. Planned Caesarean section for term breech presentation has been shown in a large randomised trial to reduce stillbirths, but the feasibility and consequences of implementing this intervention routinely in low-/middle-income countries add caveats to recommending its use. Magnesium sulphate for pre-eclampsia and eclampsia is effective in preventing eclamptic seizures, but studies have not demonstrated impact

  3. Reducing waste in Big D

    SciTech Connect

    Woods, R.

    1994-03-01

    The city of Dallas is in a unique position among major metropolitan areas of the US. Despite boasting a population of more than 1 million, which grows by 1.3% each year, and a municipal solid waste (MSW) stream averaging 1.2 million tons per year, the city -- the eighth-largest in the country -- has another 50 years of landfill disposal capacity left. This fact is even more impressive when one considers that Dallas' only municipal facility, known as the McCommas Bluff Landfill, accepted 33% more MSW in 1993 than in 1992. The positive landfill situation, however, does not mean Dallas lacks ambition for recycling and waste reduction. Last, April, the city set an aggressive goal of reducing 40% of its MSW from the landfill by 1997. To help reach this mark over the next three years, the city has banned lead-acid batteries, grass clippings, and leaves from landfills, mandated news and office paper collection, and set up a composting operation at the landfill. At present, Dallas recycles about 13% of its waste. Surprisingly, most of the residential recycling effort has been based on voluntary participation through dozens of drop-off sites scattered around the city, rather than on curbside service. The only curbside program the city is conducting is a once-per-week, blue bag pilot program involving 2,000 Dallas homes.

  4. Reducing power usage on demand

    NASA Astrophysics Data System (ADS)

    Corbett, G.; Dewhurst, A.

    2016-10-01

    The Science and Technology Facilities Council (STFC) datacentre provides large- scale High Performance Computing facilities for the scientific community. It currently consumes approximately 1.5MW and this has risen by 25% in the past two years. STFC has been investigating leveraging preemption in the Tier 1 batch farm to save power. HEP experiments are increasing using jobs that can be killed to take advantage of opportunistic CPU resources or novel cost models such as Amazon's spot pricing. Additionally, schemes from energy providers are available that offer financial incentives to reduce power consumption at peak times. Under normal operating conditions, 3% of the batch farm capacity is wasted due to draining machines. By using preempt-able jobs, nodes can be rapidly made available to run multicore jobs without this wasted resource. The use of preempt-able jobs has been extended so that at peak times machines can be hibernated quickly to save energy. This paper describes the implementation of the above and demonstrates that STFC could in future take advantage of such energy saving schemes.

  5. Neuromuscular Adaptations to Reduced Use

    NASA Technical Reports Server (NTRS)

    Ploutz-Snyder, Lori

    2009-01-01

    This viewgraph presentation reviews the studies done to reduce neuromuscular strength loss during unilateral lower limb suspension (ULLS). Since there are animals that undergo fairly long periods of muscular disuse without any or minimal muscular atrophy, there is an answer to that might be applicable to human in situations that require no muscular use to diminish the effects of muscular atrophy. Three sets of ULLS studies were reviewed indicated that muscle strength decreased more than the muscle mass. The study reviewed exercise countermeasures to combat the atrophy, including: ischemia maintained during Compound muscle action potential (CMAP), ischemia and low load exercise, Japanese kaatsu, and the potential for rehabilitation or situations where heavy loading is undesirable. Two forms of countermeasures to unloading have been successful, (1) high-load resistance training has maintained muscle mass and strength, and low load resistance training with blood flow restriction (LL(sub BFR)). The LL(sub BFR) has been shown to increase muscle mass and strength. There has been significant interest in Tourniquet training. An increase in Growth Hormone(GH) has been noted for LL(sub BFR) exercise. An experimental study with 16 subjects 8 of whom performed ULLS, and 8 of whom performed ULLS and LL(sub BFR) exercise three times per week during the ULLS. Charts show the results of the two groups, showing that performing LL(sub BFR) exercise during 30 days of ULLS can maintain muscle size and strength and even improve muscular endurance.

  6. Yolk androgens reduce offspring survival.

    PubMed Central

    Sockman, K W; Schwabl, H

    2000-01-01

    Females may favour some offspring over others by differential deposition of yolk hormones. In American kestrels (Falco sparverius), we found that yolks of eggs laid late in the sequence of a clutch had more testosterone (T) and androstenedione (A4) than yolks of first-laid eggs. To investigate the effects of these yolk androgens on nestling 'fitness', we injected both T and A4 into the yolks of first-laid eggs and compared their hatching time, nestling growth and nestling survival with those of first-laid eggs in which we injected vehicle as a control. Compared to controls, injection of T and A4 at a dose intended to increase their levels to those of later-laid eggs delayed hatching and reduced nestling growth and survival rates. Yolk androgen treatment of egg 1 had no effect on survival of siblings hatching from subsequently laid eggs. The adverse actions of yolk androgen treatment in the kestrel are in contrast to the favourable actions of yolk T treatment found previously in canaries (Serinus canaria). Additional studies are necessary in order to determine whether the deposition of yolk androgens is an adaptive form of parental favouritism or an adverse by-product of endocrine processes during egg formation. Despite its adaptive significance, such 'transgenerational' effects of steroid hormones may have helped to evolutionarily shape the hormonal mechanisms regulating reproduction. PMID:10983830

  7. Variational integrators for reduced magnetohydrodynamics

    SciTech Connect

    Kraus, Michael; Tassi, Emanuele; Grasso, Daniela

    2016-09-15

    Reduced magnetohydrodynamics is a simplified set of magnetohydrodynamics equations with applications to both fusion and astrophysical plasmas, possessing a noncanonical Hamiltonian structure and consequently a number of conserved functionals. We propose a new discretisation strategy for these equations based on a discrete variational principle applied to a formal Lagrangian. The resulting integrator preserves important quantities like the total energy, magnetic helicity and cross helicity exactly (up to machine precision). As the integrator is free of numerical resistivity, spurious reconnection along current sheets is absent in the ideal case. If effects of electron inertia are added, reconnection of magnetic field lines is allowed, although the resulting model still possesses a noncanonical Hamiltonian structure. After reviewing the conservation laws of the model equations, the adopted variational principle with the related conservation laws is described both at the continuous and discrete level. We verify the favourable properties of the variational integrator in particular with respect to the preservation of the invariants of the models under consideration and compare with results from the literature and those of a pseudo-spectral code.

  8. SRBF: Speckle reducing bilateral filtering.

    PubMed

    Balocco, Simone; Gatta, Carlo; Pujol, Oriol; Mauri, Josepa; Radeva, Petia

    2010-08-01

    Speckle noise negatively affects medical ultrasound image shape interpretation and boundary detection. Speckle removal filters are widely used to selectively remove speckle noise without destroying important image features to enhance object boundaries. In this article, a fully automatic bilateral filter tailored to ultrasound images is proposed. The edge preservation property is obtained by embedding noise statistics in the filter framework. Consequently, the filter is able to tackle the multiplicative behavior modulating the smoothing strength with respect to local statistics. The in silico experiments clearly showed that the speckle reducing bilateral filter (SRBF) has superior performances to most of the state of the art filtering methods. The filter is tested on 50 in vivo US images and its influence on a segmentation task is quantified. The results using SRBF filtered data sets show a superior performance to using oriented anisotropic diffusion filtered images. This improvement is due to the adaptive support of SRBF and the embedded noise statistics, yielding a more homogeneous smoothing. SRBF results in a fully automatic, fast and flexible algorithm potentially suitable in wide ranges of speckle noise sizes, for different medical applications (IVUS, B-mode, 3-D matrix array US).