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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. Minocycline reduces microgliosis and improves subcortical white matter function in a model of cerebral vascular disease.

    PubMed

    Manso, Yasmina; Holland, Philip R; Kitamura, Akihiro; Szymkowiak, Stefan; Duncombe, Jessica; Hennessy, Edel; Searcy, James L; Marangoni, Martina; Randall, Andrew D; Brown, Jon T; McColl, Barry W; Horsburgh, Karen

    2017-07-19

    Chronic cerebral hypoperfusion is a key mechanism associated with white matter disruption in cerebral vascular disease and dementia. In a mouse model relevant to studying cerebral vascular disease, we have previously shown that cerebral hypoperfusion disrupts axon-glial integrity and the distribution of key paranodal and internodal proteins in subcortical myelinated axons. This disruption of myelinated axons is accompanied by increased microglia and cognitive decline. The aim of the present study was to investigate whether hypoperfusion impairs the functional integrity of white matter, its relation with axon-glial integrity and microglial number, and whether by targeting microglia these effects can be improved. We show that in response to increasing durations of hypoperfusion, the conduction velocity of myelinated fibres in the corpus callosum is progressively reduced and that paranodal and internodal axon-glial integrity is disrupted. The number of microglial cells increases in response to hypoperfusion and correlates with disrupted paranodal and internodal integrity and reduced conduction velocities. Further minocycline, a proposed anti-inflammatory and microglia inhibitor, restores white matter function related to a reduction in the number of microglia. The study suggests that microglial activation contributes to the structural and functional alterations of myelinated axons induced by cerebral hypoperfusion and that dampening microglia numbers/proliferation should be further investigated as potential therapeutic benefit in cerebral vascular disease. © 2017 The Authors GLIA Published by Wiley Periodicals, Inc.

  3. 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.

  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 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

  6. Biofeedback of Real-Time Functional Magnetic Resonance Imaging Data from the Supplementary Motor Area Reduces Functional Connectivity to Subcortical Regions

    PubMed Central

    Scheinost, Dustin; Qiu, Maolin; Bhawnani, Jitendra; Lacadie, Cheryl M.; Leckman, James F.; Constable, R. Todd; Papademetris, Xenophon

    2011-01-01

    Abstract Recent studies have reported that biofeedback of real-time functional magnetic resonance imaging data can enable people to gain control of activity in specific parts of their brain and can alter functional connectivity between brain areas. Here we describe a study using biofeedback of real-time functional magnetic resonance imaging data to train healthy subjects to control activity in their supplementary motor area (SMA), a region of interest in Tourette syndrome (TS). Although a significant increase in control over the SMA during biofeedback was not found, subjects were able to exert significant control over the SMA in later biofeedback sessions despite not having control in the first biofeedback session. Further, changes were found in their resting state functional connectivity. Specifically, when comparing functional connectivity to the SMA before and after biofeedback, the strength of functional connectivity with subcortical regions was reduced after the biofeedback. This suggests that biofeedback may allow subjects to develop greater conscious control over activity in their SMA by reducing the influence of corticostriatothalamocortical loops on the region. This possibility is promising for TS, where aberrant dynamics in corticostriatothalamocortical loops have long been suspected to give rise to tic symptoms. Further studies in TS patients are needed. PMID:22432958

  7. 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.

  8. Reading and subcortical auditory function.

    PubMed

    Banai, Karen; Hornickel, Jane; Skoe, Erika; Nicol, Trent; Zecker, Steven; Kraus, Nina

    2009-11-01

    Although it is largely agreed that phonological processing deficits are a major cause of poor reading, the neural origins of phonological processing are not well understood. We now show, for the first time, that phonological decoding, measured with a test of single-nonword reading, is significantly correlated with the timing of subcortical auditory processing and also, to a lesser extent, with the robustness of subcortical representation of the harmonic content of speech, but not with pitch encoding. The relationships we observe between reading and subcortical processing fall along a continuum, with poor readers at one end and good readers at the other. These data suggest that reading skill may depend on the integrity of subcortical auditory mechanisms and are consistent with the idea that subcortical representation of the acoustic features of speech may play a role in normal reading as well as in the development of reading disorders. These data establish a significant link between subcortical auditory function and reading, thereby contributing to the understanding of the biological bases of reading. At a more general level, these findings are among the first to establish a direct relationship between subcortical sensory function and a specific cognitive skill (reading). We argue that this relationship between cortical and subcortical function could be shaped during development by the corticofugal pathway and that this cortical-subcortical link could contribute to the phonological processing deficits experienced by poor readers.

  9. 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

  10. Decreased subcortical cholinergic arousal in focal seizures

    PubMed Central

    Motelow, Joshua E.; Li, Wei; Zhan, Qiong; Mishra, Asht M.; Sachdev, Robert N. S.; Liu, Geoffrey; Gummadavelli, Abhijeet; Zayyad, Zaina; Lee, Hyun Seung; Chu, Victoria; Andrews, John P.; Englot, Dario J.; Herman, Peter; Sanganahalli, Basavaraju G.; Hyder, Fahmeed; Blumenfeld, Hal

    2015-01-01

    SUMMARY Impaired consciousness in temporal lobe seizures has a major negative impact on quality of life. The prevailing view holds that this disorder impairs consciousness by seizure spread to the bilateral temporal lobes. We propose instead that seizures invade subcortical regions and depress arousal, causing impairment through decreases rather than through increases in activity. Using functional magnetic resonance imaging in a rodent model, we found increased activity in regions known to depress cortical function including lateral septum and anterior hypothalamus. Importantly, we found suppression of intralaminar thalamic and brainstem arousal systems and suppression of the cortex. At a cellular level, we found reduced firing of identified cholinergic neurons in the brainstem pedunculopontine tegmental nucleus and basal forebrain. Finally, we used enzyme-based amperometry to demonstrate reduced cholinergic neurotransmission in both cortex and thalamus. Decreased subcortical arousal is a novel mechanism for loss of consciousness in focal temporal lobe seizures. PMID:25654258

  11. 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

  12. 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.

  13. 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.

  14. 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

  15. [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.

  16. 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.

  17. Subcortical Control of Precision Grip after Human Spinal Cord Injury

    PubMed Central

    Bunday, Karen L.; Tazoe, Toshiki; Rothwell, John C.

    2014-01-01

    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. PMID:24849366

  18. 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

  19. 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. Copyright © 2015 the American Physiological Society.

  20. 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.

  1. Mapping abnormal subcortical brain morphometry in an elderly HIV + cohort

    PubMed Central

    Wade, Benjamin S.C.; Valcour, Victor G.; Wendelken-Riegelhaupt, Lauren; Esmaeili-Firidouni, Pardis; Joshi, Shantanu H.; Gutman, Boris A.; Thompson, Paul M.

    2015-01-01

    Over 50% of HIV + individuals exhibit neurocognitive impairment and subcortical atrophy, but the profile of brain abnormalities associated with HIV is still poorly understood. Using surface-based shape analyses, we mapped the 3D profile of subcortical morphometry in 63 elderly HIV + participants and 31 uninfected controls. The thalamus, caudate, putamen, pallidum, hippocampus, amygdala, brainstem, accumbens, callosum and ventricles were segmented from high-resolution MRIs. To investigate shape-based morphometry, we analyzed the Jacobian determinant (JD) and radial distances (RD) defined on each region's surfaces. We also investigated effects of nadir CD4 + T-cell counts, viral load, time since diagnosis (TSD) and cognition on subcortical morphology. Lastly, we explored whether HIV + participants were distinguishable from unaffected controls in a machine learning context. All shape and volume features were included in a random forest (RF) model. The model was validated with 2-fold cross-validation. Volumes of HIV + participants' bilateral thalamus, left pallidum, left putamen and callosum were significantly reduced while ventricular spaces were enlarged. Significant shape variation was associated with HIV status, TSD and the Wechsler adult intelligence scale. HIV + people had diffuse atrophy, particularly in the caudate, putamen, hippocampus and thalamus. Unexpectedly, extended TSD was associated with increased thickness of the anterior right pallidum. In the classification of HIV + participants vs. controls, our RF model attained an area under the curve of 72%. PMID:26640768

  2. Re-expression of pro-fibrotic, embryonic preserved mediators in irradiated arterial vessels of the head and neck region.

    PubMed

    Möbius, Patrick; Preidl, Raimund H M; Weber, Manuel; Amann, Kerstin; Neukam, Friedrich W; Wehrhan, Falk

    2017-08-15

    Surgical treatment of head and neck malignancies frequently includes microvascular free tissue transfer. Preoperative radiotherapy increases postoperative fibrosis-related complications up to transplant loss. Fibrogenesis is associated with re-expression of embryonic preserved tissue developmental mediators: osteopontin (OPN), regulated by sex-determining region Y‑box 9 (Sox9), and homeobox A9 (HoxA9) play important roles in pathologic tissue remodeling and are upregulated in atherosclerotic vascular lesions; dickkopf-1 (DKK1) inhibits pro-fibrotic and atherogenic Wnt signaling. We evaluated the influence of irradiation on expression of these mediators in arteries of the head and neck region. DKK1, HoxA9, OPN, and Sox9 expression was examined immunohistochemically in 24 irradiated and 24 nonirradiated arteries of the lower head and neck region. The ratio of positive cells to total cell number (labeling index) in the investigated vessel walls was assessed semiquantitatively. DKK1 expression was significantly decreased, whereas HoxA9, OPN, and Sox9 expression were significantly increased in irradiated compared to nonirradiated arterial vessels. Preoperative radiotherapy induces re-expression of embryonic preserved mediators in arterial vessels and may thus contribute to enhanced activation of pro-fibrotic downstream signaling leading to media hypertrophy and intima degeneration comparable to fibrotic development steps in atherosclerosis. These histopathological changes may be promoted by HoxA9-, OPN-, and Sox9-related inflammation and vascular remodeling, supported by downregulation of anti-fibrotic DKK1. Future pharmaceutical strategies targeting these vessel alterations, e. g., bisphosphonates, might reduce postoperative complications in free tissue transfer.

  3. 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.

  4. Dysphagia Post Subcortical and Supratentorial Stroke.

    PubMed

    Wan, Ping; Chen, Xuhui; Zhu, Lequn; Xu, Shuangjin; Huang, Li; Li, Xiangcui; Ye, Qing; Ding, Ruiying

    2016-01-01

    Studies have recognized that the damage in the subcortical and supratentorial regions may affect voluntary and involuntary aspects of the swallowing function. The current study attempted to explore the dysphagia characteristics in patients with subcortical and supratentorial stroke. Twelve post first or second subcortical and supratentorial stroke patients were included in the study. The location of the stroke was ascertained by computed tomography and magnetic resonance imaging. The characteristics of swallowing disorder were assessed by video fluoroscopic swallowing assessment/fiberoptic endoscopic evaluation of swallowing. The following main parameters were analyzed: oral transit time, pharyngeal delay time, presence of cricopharyngeal muscle achalasia (CMA), distance of laryngeal elevation, the amounts of vallecular residue and pyriform sinus residue (PSR), and the extent of pharyngeal contraction. Eighty-three percent of the 12 patients were found suffering from pharyngeal dysphagia, with 50% having 50%-100% PSRs, 50% having pharyngeal delay, and 41.6% cases demonstrating CMA. Simple regression analysis showed PSRs were most strongly associated with CMA. Pharyngeal delay in the study can be caused by infarcts of basal ganglia/thalamus, infarcts of sensory tract, infarcts of swallowing motor pathways in the centrum semiovale, or a combination of the three. Subcortical and supratentorial stroke may result in pharyngeal dysphagia such as PSR and pharyngeal delay. PSR was mainly caused by CMA. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  5. 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.

  6. 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

  7. Subcortical (18) F-AV-1451 binding patterns in progressive supranuclear palsy.

    PubMed

    Cho, Hanna; Choi, Jae Yong; Hwang, Mi Song; Lee, Seung Ha; Ryu, Young Hoon; Lee, Myung Sik; Lyoo, Chul Hyoung

    2017-01-01

    Accumulation of cortical and subcortical tau pathology is the primary pathological substrate for progressive supranuclear palsy (PSP). (18) F-AV-1451, a radiotracer that binds to the pathological tau protein, may be helpful for in vivo visualization and quantitation of tau pathology in PSP. The objectives of this study were to investigate cortical and subcortical (18) F-AV-1451 binding patterns in patients with PSP. We recruited 14 PSP patients and compared their cortical and subcortical binding patterns in (18) F-AV-1451 positron emission tomography (PET) studies with those of 15 Parkinson's disease (PD) patients and 15 healthy controls. In both the PD and PSP groups, subcortical (18) F-AV-1451 binding did not correlate with the severity of motor dysfunctions, and cortical binding did not differ between the controls and each patient group. However, the PSP patients showed greater (18) F-AV-1451 binding in the putamen, globus pallidus, subthalamic nucleus, and dentate nucleus when compared with the controls, whereas the PD patients showed lower (18) F-AV-1451 binding in the substantia nigra than controls. The PSP and PD patients showed distinct subcortical (18) F-AV-1451 binding patterns reflecting subcortical tau pathology in PSP and reduced nigral neuromelanin in PD. However, there was no correlation with the severity of motor dysfunction, no cortical regions with increased binding in PSP patients, and variable degrees of subcortical binding even in the controls. Therefore, the (18) F-AV-1451 PET may be less than ideal for assessing tau pathology in PSP. Further studies will be required to validate the clinical correlation and to understand the clinical utility of (18) F-AV-1451 PET for PSP patients. © 2016 International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder Society.

  8. 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

  9. Subcortical cytoskeleton periodicity throughout the nervous system.

    PubMed

    D'Este, Elisa; Kamin, Dirk; Velte, Caroline; Göttfert, Fabian; Simons, Mikael; Hell, Stefan W

    2016-03-07

    Superresolution fluorescence microscopy recently revealed a ~190 nm periodic cytoskeleton lattice consisting of actin, spectrin, and other proteins underneath the membrane of cultured hippocampal neurons. Whether the periodic cytoskeleton lattice is a structural feature of all neurons and how it is modified when axons are ensheathed by myelin forming glial cells is not known. Here, STED nanoscopy is used to demonstrate that this structure is a commonplace of virtually all neuron types in vitro. To check how the subcortical meshwork is modified during myelination, we studied sciatic nerve fibers from adult mice. Periodicity of both actin and spectrin was uncovered at the internodes, indicating no substantial differences between unmyelinated and myelinated axons. Remarkably, the actin/spectrin pattern was also detected in glial cells such as cultured oligodendrocyte precursor cells. Altogether our work shows that the periodic subcortical cytoskeletal meshwork is a fundamental characteristic of cells in the nervous system and is not a distinctive feature of neurons, as previously thought.

  10. 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.

  11. Subcortical structure alterations impact language processing in individuals with schizophrenia and those at high genetic risk.

    PubMed

    Li, Xiaobo; Black, Margaret; Xia, Shugao; Zhan, Chenyang; Bertisch, Hilary C; Branch, Craig A; DeLisi, Lynn E

    2015-12-01

    Cortical structural and functional anomalies have been found to associate with language impairments in both schizophrenia patients and genetic high risk individuals for developing schizophrenia. However, subcortical structures that contribute to language processing haven't been well studied in this population, and thus became the main objective of this study. We examined structural MRI data from 20 patients with schizophrenia, 21 individuals at genetic high risk, and 48 controls. Surface shape and volume differences of 6 subcortical structures that are involved in language processing, including nuclei pallidum, putamen, caudate, amygdala, thalamus, and hippocampus from both hemispheres, were compared between groups. Performance scores of language-associated cognitive tests were obtained to identify relationships of subcortical structures to language-related behaviors. Significantly reduced volumes of both the left and right side caudate nuclei, thalami and right side amygdala were shown in patients when compared with controls. Very interestingly, the high risk group demonstrated significantly increased correlations between volumes of left side pallidum nucleus and bilateral thalami and language-related cognitive test scores when compared to controls. This study furthers our understanding of subcortical structural alterations in schizophrenia and high risk individuals, and suggests the contribution of subcortical structures to the language impairments that may serve as an early sign for impending development of schizophrenia. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Subcortical Correlates of Individual Differences in Aptitude

    PubMed Central

    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). PMID:24586770

  13. 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).

  14. 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

  15. DNA demethylation induces SALL4 gene re-expression in subgroups of hepatocellular carcinoma associated with Hepatitis B or C virus infection.

    PubMed

    Fan, H; Cui, Z; Zhang, H; Mani, S K; Diab, A; Lefrancois, L; Fares, N; Merle, P; Andrisani, O

    2017-04-27

    Sal-like protein 4 (SALL4), an embryonic stem cell transcriptional regulator, is re-expressed by an unknown mechanism in poor prognosis hepatocellular carcinoma (HCC), often associated with chronic hepatitis B virus (HBV) infection. Herein, we investigated the mechanism of SALL4 re-expression in HBV-related HCCs. We performed bisulfite sequencing PCR of genomic DNA isolated from HBV-related HCCs and HBV replicating cells, and examined DNA methylation of a CpG island located downstream from SALL4 transcriptional start site (TSS). HBV-related HCCs expressing increased SALL4 exhibited demethylation of specific CpG sites downstream of SALL4 TSS. Similarly, SALL4 re-expression and demethylation of these CpGs was observed in HBV replicating cells. SALL4 is also re-expressed in poor prognosis HCCs of other etiologies. Indeed, increased SALL4 expression in hepatitis C virus-related HCCs correlated with demethylation of these CpG sites. To understand how CpG demethylation downstream of SALL4 TSS regulates SALL4 transcription, we quantified by chromatin immunoprecipitation (ChIP) assays RNA polymerase II occupancy of SALL4 gene, as a function of HBV replication. In absence of HBV replication, RNA polymerase II associated with SALL4 exon1. By contrast, in HBV replicating cells RNA polymerase II occupancy of all SALL4 exons increased, suggesting CpG demethylation downstream from SALL4 TSS influences SALL4 transcriptional elongation. Intriguingly, demethylated CpGs downstream from SALL4 TSS are within binding sites of octamer-binding transcription factor 4 (OCT4) and signal transducer and activator of transcription3 (STAT3). ChIP assays confirmed occupancy of these sites by OCT4 and STAT3 in HBV replicating cells, and sequential ChIP assays demonstrated co-occupancy with chromatin remodeling BRG1/Brahma-associated factors. BRG1 knockdown reduced SALL4 expression, whereas BRG1 overexpression increased SALL4 transcription in HBV replicating cells. We conclude demethylation of Cp

  16. Subcortical brain atrophy in Gulf War Illness.

    PubMed

    Christova, Peka; James, Lisa M; Engdahl, Brian E; Lewis, Scott M; Carpenter, Adam F; Georgopoulos, Apostolos P

    2017-06-20

    Gulf War Illness (GWI) is a multisystem disorder that has affected a substantial number of veterans who served in the 1990-1991 Gulf War. The brain is prominently affected, as manifested by the presence of neurological, cognitive and mood symptoms. Although brain dysfunction in GWI has been well documented (EBioMedicine 12:127-32, 2016), abnormalities in brain structure have been debated. Here we report a substantial (~10%) subcortical brain atrophy in GWI comprising mainly the brainstem, cerebellum and thalamus, and, to a lesser extent, basal ganglia, amygdala and diencephalon. The highest atrophy was observed in the brainstem, followed by left cerebellum and right thalamus, then by right cerebellum and left thalamus. These findings indicate graded atrophy of regions anatomically connected through the brainstem via the crossed superior cerebellar peduncle (left cerebellum → right thalamus, right cerebellum → left thalamus). This distribution of atrophy, together with the observed systematic reduction in volume of other subcortical areas (basal ganglia, amygdala and diencephalon), resemble the distribution of atrophy seen in toxic encephalopathy (Am J Neuroradiol 13:747-760, 1992) caused by a variety of substances, including organic solvents. Given the potential exposure of Gulf War veterans to "a wide range of biological and chemical agents including sand, smoke from oil-well fires, paints, solvents, insecticides, petroleum fuels and their combustion products, organophosphate nerve agents, pyridostigmine bromide, …" (Institute of Medicine National Research Council. Gulf War and Health: Volume 1. Depleted uranium, pyridostigmine bromide, sarin, and vaccines. National Academies Press, Washington DC, 2000), it is reasonable to suppose that such exposures, alone or in combination, could underlie the subcortical atrophy observed.

  17. Sex differences in auditory subcortical function.

    PubMed

    Krizman, Jennifer; Skoe, Erika; Kraus, Nina

    2012-03-01

    Sex differences have been demonstrated in the peripheral auditory system as well as in higher-level cognitive processing. Here, we aimed to determine if the subcortical response to a complex auditory stimulus is encoded differently between the sexes. Using electrophysiological techniques, we assessed the auditory brainstem response to a synthesized stop-consonant speech syllable [da] in 76 native-English speaking, young adults (38 female). Timing and frequency components of the response were compared between males and females to determine which aspects of the response are affected by sex. A dissimilarity between males and females was seen in the neural response to the components of the speech stimulus that change rapidly over time; but not in the slower changing, lower frequency information in the stimulus. We demonstrate that, in agreement with the click-evoked brainstem response, females have earlier peaks relative to males in the subcomponents of the response representing the onset of the speech sound. In contrast, the response peaks comprising the frequency-following response, which encode the fundamental frequency (F(0)) of the stimulus, as well as the spectral amplitude of the response to the F(0), is not affected by sex. Notably, the higher-frequency elements of the speech syllable are encoded differently between males and females, with females having greater representation of spectrotemporal information for frequencies above the F(0). Our results provide a baseline for interpreting the higher incidence of language impairment (e.g. dyslexia, autism, specific language impairment) in males, and the subcortical deficits associated with these disorders. These results parallel the subcortical encoding patterns that are documented for good and poor readers in that poor readers differ from good readers on encoding fast but not slow components of speech. This parallel may thus help to explain the higher incidence of reading impairment in males compared to females

  18. 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.

  19. Changes in cortico-subcortical and subcortico-subcortical connectivity impact cognitive control to emotional cues across development

    PubMed Central

    Cohen, Alexandra O.; Dreyfuss, Michael F. W.; Casey, B. J.

    2016-01-01

    The capacity to suppress inappropriate thoughts, emotions and actions in favor of appropriate ones shows marked changes throughout childhood and adolescence. Most research has focused on pre-frontal circuit development to explain these changes. Yet, subcortical circuitry involving the amygdala and ventral striatum (VS) has been shown to modulate cue-triggered motivated behaviors in rodents. The nature of the interaction between these two subcortical regions in humans is less well understood, especially during development when there appears to be heightened sensitivity to emotional cues. In the current study, we tested how task-based cortico-subcortical and subcortico-subcortical functional connectivity in 155 participants ages from 5 to 32 impacted cognitive control performance on an emotional go/nogo task. Functional connectivity between the amygdala and VS was inversely correlated with age and predicted cognitive control to emotional cues, when controlling for performance to neutral cues. In contrast, increased medial pre-frontal-amygdala connectivity was associated with better cognitive control to emotional cues and this cortical-subcortical connectivity mediated the association between amygdala-VS connectivity and emotional cognitive control. These findings suggest a dissociation in how subcortical-subcortical and cortical-subcortical connectivity impact cognitive control across development. PMID:27445212

  20. Sequencing of mRNA identifies re-expression of fetal splice variants in cardiac hypertrophy.

    PubMed

    Ames, E G; Lawson, M J; Mackey, A J; Holmes, J W

    2013-09-01

    Cardiac hypertrophy has been well-characterized at the level of transcription. During cardiac hypertrophy, genes normally expressed primarily during fetal heart development are re-expressed, and this fetal gene program is believed to be a critical component of the hypertrophic process. Recently, alternative splicing of mRNA transcripts has been shown to be temporally regulated during heart development, leading us to consider whether fetal patterns of splicing also reappear during hypertrophy. We hypothesized that patterns of alternative splicing occurring during heart development are recapitulated during cardiac hypertrophy. Here we present a study of isoform expression during pressure-overload cardiac hypertrophy induced by 10 days of transverse aortic constriction (TAC) in rats and in developing fetal rat hearts compared to sham-operated adult rat hearts, using high-throughput sequencing of poly(A) tail mRNA. We find a striking degree of overlap between the isoforms expressed differentially in fetal and pressure-overloaded hearts compared to control: forty-four percent of the isoforms with significantly altered expression in TAC hearts are also expressed at significantly different levels in fetal hearts compared to control (P<0.001). The isoforms that are shared between hypertrophy and fetal heart development are significantly enriched for genes involved in cytoskeletal organization, RNA processing, developmental processes, and metabolic enzymes. Our data strongly support the concept that mRNA splicing patterns normally associated with heart development recur as part of the hypertrophic response to pressure overload. These findings suggest that cardiac hypertrophy shares post-transcriptional as well as transcriptional regulatory mechanisms with fetal heart development. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. Epidrug mediated re-expression of miRNA targeting the HMGA transcripts in pituitary cells.

    PubMed

    Kitchen, Mark O; Yacqub-Usman, Kiren; Emes, Richard D; Richardson, Alan; Clayton, Richard N; Farrell, William E

    2015-10-01

    Transgenic mice overexpressing the high mobility group A (HMGA) genes, Hmga1 or Hmga2 develop pituitary tumours and their overexpression is also a frequent finding in human pituitary adenomas. In some cases, increased expression of HMGA2 but not that of HMGA1 is consequent to genetic perturbations. However, recent studies show that down-regulation of microRNA (miRNA), that contemporaneously target the HMGA1 and HMGA2 transcripts, are associated with their overexpression. In a cohort of primary pituitary adenoma we determine the impact of epigenetic modifications on the expression of HMGA-targeting miRNA. For these miRNAs, chromatin immunoprecipitations showed that transcript down-regulation is correlated with histone tail modifications associated with condensed silenced genes. The functional impact of epigenetic modification on miRNA expression was determined in the rodent pituitary cell line, GH3. In these cells, histone tail, miRNA-associated, modifications were similar to those apparent in human adenoma and likely account for their repression. Indeed, challenge of GH3 cells with the epidrugs, zebularine and TSA, led to enrichment of the histone modification, H3K9Ac, associated with active genes, and depletion of the modification, H3K27me3, associated with silent genes and re-expression of HMGA-targeting miRNA. Moreover, epidrugs challenges were also associated with a concomitant decrease in hmga1 transcript and protein levels and concurrent increase in bmp-4 expression. These findings show that the inverse relationship between HMGA expression and targeting miRNA is reversible through epidrug interventions. In addition to showing a mechanistic link between epigenetic modifications and miRNA expression these findings underscore their potential as therapeutic targets in this and other diseases.

  2. 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

  3. 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.

  4. Inflammatory demyelination alters subcortical visual circuits.

    PubMed

    Araújo, Sheila Espírito Santo; Mendonça, Henrique Rocha; Wheeler, Natalie A; Campello-Costa, Paula; Jacobs, Kimberle M; Gomes, Flávia C A; Fox, Michael A; Fuss, Babette

    2017-08-18

    Multiple sclerosis (MS) is an inflammatory demyelinating disease classically associated with axonal damage and loss; more recently, however, synaptic changes have been recognized as additional contributing factors. An anatomical area commonly affected in MS is the visual pathway; yet, changes other than those associated with inflammatory demyelination of the optic nerve, i.e., optic neuritis, have not been described in detail. Adult mice were subjected to a diet containing cuprizone to mimic certain aspects of inflammatory demyelination as seen in MS. Demyelination and inflammation were assessed by real-time polymerase chain reaction and immunohistochemistry. Synaptic changes associated with inflammatory demyelination in the dorsal lateral geniculate nucleus (dLGN) were determined by immunohistochemistry, Western blot analysis, and electrophysiological field potential recordings. In the cuprizone model, demyelination was observed in retinorecipient regions of the subcortical visual system, in particular the dLGN, where it was found accompanied by microglia activation and astrogliosis. In contrast, anterior parts of the pathway, i.e., the optic nerve and tract, appeared largely unaffected. Under the inflammatory demyelinating conditions, as seen in the dLGN of cuprizone-treated mice, there was an overall decrease in excitatory synaptic inputs from retinal ganglion cells. At the same time, the number of synaptic complexes arising from gamma-aminobutyric acid (GABA)-generating inhibitory neurons was found increased, as were the synapses that contain the N-methyl-D-aspartate receptor (NMDAR) subunit GluN2B and converge onto inhibitory neurons. These synaptic changes were functionally found associated with a shift toward an overall increase in network inhibition. Using the cuprizone model of inflammatory demyelination, our data reveal a novel form of synaptic (mal)adaption in the CNS that is characterized by a shift of the excitation/inhibition balance toward inhibitory

  5. 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.

  6. Quantity language speakers show enhanced subcortical processing.

    PubMed

    Dawson, Caitlin; Aalto, Daniel; Šimko, Juraj; Putkinen, Vesa; Tervaniemi, Mari; Vainio, Martti

    2016-07-01

    The complex auditory brainstem response (cABR) can reflect language-based plasticity in subcortical stages of auditory processing. It is sensitive to differences between language groups as well as stimulus properties, e.g. intensity or frequency. It is also sensitive to the synchronicity of the neural population stimulated by sound, which results in increased amplitude of wave V. Finnish is a full-fledged quantity language, in which word meaning is dependent upon duration of the vowels and consonants. Previous studies have shown that Finnish speakers have enhanced behavioural sound duration discrimination ability and larger cortical mismatch negativity (MMN) to duration change compared to German and French speakers. The next step is to find out whether these enhanced duration discrimination abilities of quantity language speakers originate at the brainstem level. Since German has a complementary quantity contrast which restricts the possible patterns of short and long vowels and consonants, the current experiment compared cABR between nonmusician Finnish and German native speakers using seven short complex stimuli. Finnish speakers had a larger cABR peak amplitude than German speakers, while the peak onset latency was only affected by stimulus intensity and spectral band. The results suggest that early cABR responses are better synchronised for Finns, which could underpin the enhanced duration sensitivity of quantity language speakers. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  7. 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.

  8. 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

  9. Morphological MRI characteristics of recent small subcortical infarcts.

    PubMed

    Gattringer, Thomas; Eppinger, Sebastian; Pinter, Daniela; Pirpamer, Lukas; Berghold, Andrea; Wünsch, Gerit; Ropele, Stefan; Wardlaw, Joanna M; Enzinger, Christian; Fazekas, Franz

    2015-10-01

    New imaging criteria for recent small subcortical infarcts have recently been proposed, replacing the earlier term 'lacunar infarction', but their applicability and impact on lesion selection is yet unknown. To collect information on the morphologic characteristics and variability of recent small subcortical infarcts on magnetic resonance imaging in regard to lesion location and demographic variables. We identified all patients with acute stroke and cerebral magnetic resonance imaging from 2008 to 2013 in our hospital database and selected those with a single recent small subcortical infarct defined by an estimated maximal axial diameter of 20 mm. Recent small subcortical infarcts were segmented on diffusion-weighted imaging and fluid-attenuated inversion recovery sequence to calculate the largest axial and longitudinal diameter and lesion volume. We assessed morphometric differences of recent small subcortical infarcts regarding location and demographic variables and the impact of different recent small subcortical infarct definitions on lesion selection. Three hundred forty-four patients (median age 72; range 25-92 years, 65% male) were selected. Most recent small subcortical infarcts were located in the basal ganglia (n = 111), followed by pons (n = 92), thalamus (n = 77), and centrum semiovale (n = 64). Quantitative measurements confirmed visual assessment of the axial diameter in 95%. All morphometric variables were strongly intercorrelated and comparable on diffusion-weighted imaging and fluid-attenuated inversion recovery sequence. Recent small subcortical infarcts in the basal ganglia were significantly larger both in the axial and longitudinal direction compared with other regions. Dichotomization of recent small subcortical infarcts according to axial (≤ / >15 mm) or longitudinal (≤ / >20 mm) sizes resulted in different regional frequencies and distributions. Age, gender, and time from stroke onset to magnetic resonance imaging

  10. 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.

  11. 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.

  12. 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

  13. Neurobehavioral dysfunction in patients with subcortical vascular mild cognitive impairment and subcortical vascular dementia.

    PubMed

    Chin, Juhee; Seo, Sang Won; Kim, Sook Hui; Park, Aram; Ahn, Hyun-Jung; Lee, Byung Hwa; Kang, Sue J; Na, Duk L

    2012-01-01

    Amnestic mild cognitive impairment (MCI) is considered to be a prodromal stage of Alzheimer's disease. Likewise, subcortical vascular MCI (svMCI) is considered as a prodromal stage of subcortical vascular dementia (SVaD). The objective of this study was to investigate neuropsychiatric features in patients with svMCI compared to healthy controls and patients with SVaD. We evaluated 31 patients with svMCI, 42 with SVaD, and 28 healthy controls who underwent neuropsychiatric assessments using the Neuropsychiatric Inventory (NPI) and the Frontal Behavioral Inventory (FBI). On both the NPI and FBI, SVaD patients had the most severe neuropsychiatric symptoms, followed by svMCI patients and then healthy controls, suggesting that svMCI might be a prodromal stage of SVaD in terms of neuropsychiatric abnormalities. When we compared the differences of mean scores between negative and positive symptoms in FBI, negative symptoms tended to be more predominant than positive symptoms in both svMCI and SVaD patients, but the tendency was stronger in SVaD patients than in svMCI patients. These results suggest that vascular cognitive impairment with small vessel disease would start with both negative and positive neuropsychiatric symptoms and progress to present more severe negative symptoms. These behavioral ratings may be useful for early detection of vascular cognitive impairment associated with small vessel disease.

  14. 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

  15. Subcortical volumetric abnormalities in bipolar disorder.

    PubMed

    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

    2016-12-01

    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.

  16. 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.

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. Intraoperative Subcortical Fiber Mapping with Subcortico-Cortical Evoked Potentials.

    PubMed

    Enatsu, Rei; Kanno, Aya; Ohtaki, Shunya; Akiyama, Yukinori; Ochi, Satoko; Mikuni, Nobuhiro

    2016-02-01

    During brain surgery, there are difficulties associated with identifying subcortical fibers with no clear landmarks. We evaluated the usefulness of cortical evoked potentials with subcortical stimuli (subcortico-cortical evoked potential [SCEP]) in identifying subcortical fibers intraoperatively. We used SCEP to identify the pyramidal tract in 4 patients, arcuate fasciculus in 1 patient, and both in 2 patients during surgical procedures. After resection, a 1 × 4-electrode plate was placed on the floor of the removal cavity and 1-Hz alternating electrical stimuli were delivered to this electrode. A 4 × 5 recording electrode plate was placed on the central cortical areas to map the pyramidal tract and temporoparietal cortical areas for the arcuate fasciculus. SCEPs were obtained by averaging electrocorticograms time locked to the stimulus onset. The subcortical stimulation within 15 mm of the target fiber induced cortical evoked potentials in the corresponding areas, whereas the stimulation apart from 20 mm did not. Five patients showed transient worsening of neurologic symptoms after surgery. However, all patients recovered. SCEP was useful for identifying subcortical fibers and confirmed the preservation of these fibers. This technique is expected to contribute to the effectiveness and safety of resective surgery in patients with lesions close to eloquent areas. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Re-expression of the developmental gene Pax-2 during experimental acute tubular necrosis in mice 1.

    PubMed

    Imgrund, M; Gröne, E; Gröne, H J; Kretzler, M; Holzman, L; Schlöndorff, D; Rothenpieler, U W

    1999-10-01

    The transcription factor Pax-2 is known to play a key regulatory role during embryonic development of the nervous and excretory systems in mammals and flies. During mouse kidney development, Pax-2 is expressed in the undifferentiated mesenchyme in response to ureter induction and continues to be expressed in the developing comma- and s-shaped bodies. These structures harbor the immediate precursors of the proximal tubular epithelial cells. Pax-2 expression is down-regulated as the differentiation of the functional units of the nephron proceeds. In the adult mammalian kidney, the Pax-2 protein is detectable exclusively in the epithelium of the collecting ducts. We sought to test the hypothesis that tissue regeneration is characterized by re-expression of developmentally important regulatory genes such as Pax-2. The expression pattern of Pax-2 in kidneys after experimentally-induced acute tubular necrosis caused by intraperitoneally injected folic acid in mice was tested by indirect immunofluorescence, Western blotting, reverse transcriptase-polymerase chain reaction, and in situ hybridization analysis. A transient, temporally and locally restricted re-expression of Pax-2 in regenerating proximal tubular epithelial cells was observed following kidney damage. These data indicate that during the regeneration processes, developmental paradigms may be recapitulated in order to restore mature kidney function.

  3. 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

  4. 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.

  5. Apraxia related with subcortical lesions due to cerebrovascular disease.

    PubMed

    Tabaki, N E; Vikelis, M; Besmertis, L; Vemmos, K; Stathis, P; Mitsikostas, D D

    2010-07-01

    To examine whether ideomotor apraxia exists in patients with subcortical ischemic lesions. A matched-control, prospective and multi-centered research design was used. Ideomotor apraxia, anxiety and depression were assessed by the Movement Imitation Test and the Hamilton scales, respectively. Forty two consecutive patients with subcortical ischemic stroke and an equal number of healthy participants, matched in age and sex were included. Paired-sample t-tests showed that patients had significantly more apractic elements in their movements (t = 5.03, P < 0.01), higher anxiety (t = -2.55, P = 0.0014) and depression levels (t = -2.61, P = 0.012) than their healthy matched participants. Participants with higher anxiety and depression scores performed worse on the Movement Imitation Test. Ischemic damage of subcortical modular systems may affect praxis.

  6. 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

  7. 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

  8. 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.

  9. Subcortical atrophy is associated with cognitive impairment in mild Parkinson disease: a combined investigation of volumetric changes, cortical thickness, and vertex-based shape analysis.

    PubMed

    Mak, E; Bergsland, N; Dwyer, M G; Zivadinov, R; Kandiah, N

    2014-12-01

    The involvement of subcortical deep gray matter and cortical thinning associated with mild Parkinson disease remains poorly understood. We assessed cortical thickness and subcortical volumes in patients with Parkinson disease without dementia and evaluated their associations with cognitive dysfunction. The study included 90 patients with mild Parkinson disease without dementia. Neuropsychological assessments classified the sample into patients with mild cognitive impairment (n = 25) and patients without cognitive impairment (n = 65). Volumetric data for subcortical structures were obtained by using the FMRIB Integrated Registration and Segmentation Tool while whole-brain, gray and white matter volumes were estimated by using Structural Image Evaluation, with Normalization of Atrophy. Vertex-based shape analyses were performed to investigate shape differences in subcortical structures. Vertex-wise group differences in cortical thickness were also assessed. Volumetric comparisons between Parkinson disease with mild cognitive impairment and Parkinson disease with no cognitive impairment were performed by using ANCOVA. Associations of subcortical structures with both cognitive function and disease severity were assessed by using linear regression models. Compared with Parkinson disease with no cognitive impairment, Parkinson disease with mild cognitive impairment demonstrated reduced volumes of the thalamus (P = .03) and the nucleus accumbens (P = .04). Significant associations were found for the nucleus accumbens and putamen with performances on the attention/working memory domains (P < .05) and nucleus accumbens and language domains (P = .04). The 2 groups did not differ in measures of subcortical shape or in cortical thickness. Patients with Parkinson disease with mild cognitive impairment demonstrated reduced subcortical volumes, which were associated with cognitive deficits. The thalamus, nucleus accumbens, and putamen may serve as potential biomarkers for

  10. 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.

  11. 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.

  12. 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…

  13. 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…

  14. 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…

  15. 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…

  16. Cortical connectivity after subcortical stroke assessed with functional magnetic resonance imaging.

    PubMed

    Grefkes, Christian; Nowak, Dennis A; Eickhoff, Simon B; Dafotakis, Manuel; Küst, Jutta; Karbe, Hans; Fink, Gereon R

    2008-02-01

    This study aimed at identifying the impact of subcortical stroke on the interaction of cortical motor areas within and across hemispheres during the generation of voluntary hand movements. Twelve subacute stroke patients with a subcortical ischemic lesion and 12 age-matched control subjects were scanned using 3-Tesla functional magnetic resonance imaging. Subjects performed visually paced hand movements with their left, right, or both hands. Changes of effective connectivity among a bilateral network of core motor regions comprising M1, lateral premotor cortex, and the supplementary motor area (SMA) were assessed using dynamic causal modeling. The data showed significant disturbances in the effective connectivity of motor areas in the patients group: Independently from hand movements, the intrinsic neural coupling between ipsilesional SMA and M1, and the interhemispheric coupling of both SMAs was significantly reduced. Furthermore, movements of the stroke-affected hand showed additional inhibitory influences from contralesional to ipsilesional M1 that correlated with the degree of motor impairment. For bimanual movements, interhemispheric communication between ipsilesional SMA and contralesional M1 was significantly reduced, which also correlated with impaired bimanual performance. The motor deficit of patients with a single subcortical lesion is associated with pathological interhemispheric interactions among key motor areas. The data suggest that a dysfunction between ipsilesional and contralesional M1, and between ipsilesional SMA and contralesional M1 underlies hand motor disability after stroke. Assessing effective connectivity by means of functional magnetic resonance imaging and dynamic causal modeling might be used in the future for the evaluation of interventions promoting recovery of function.

  17. Patterns in Cortical Connectivity for Determining Outcomes in Hand Function after Subcortical Stroke

    PubMed Central

    Yin, Dazhi; Song, Fan; Xu, Dongrong; Peterson, Bradley S.; Sun, Limin; Men, Weiwei; Yan, Xu; Fan, Mingxia

    2012-01-01

    Background and Purpose Previous studies have noted changes in resting-state functional connectivity during motor recovery following stroke. However, these studies always uncover various patterns of motor recovery. Moreover, subgroups of stroke patients with different outcomes in hand function have rarely been studied. Materials and Methods We selected 24 patients who had a subcortical stroke in the left motor pathway and displayed only motor deficits. The patients were divided into two subgroups: completely paralyzed hands (CPH) (12 patients) and partially paralyzed hands (PPH) (12 patients). Twenty-four healthy controls (HC) were also recruited. We performed functional connectivity analysis in both the ipsilesional and contralesional primary motor cortex (M1) to explore the differences in the patterns between each pair of the three diagnostic groups. Results Compared with the HC, the PPH group displays reduced connectivity of both the ipsilesional and contralesional M1 with bilateral prefrontal gyrus and contralesional cerebellum posterior lobe. The connectivity of both the ipsilesional and contralesional M1 with contralateral primary sensorimotor cortex was reduced in the CPH group. Additionally, the connectivity of the ipsilesional M1 with contralesional postcentral gyrus, superior parietal lobule and ipsilesional inferior parietal lobule was reduced in the CPH group compared with the PPH group. Moreover, the connectivity of these regions was positively correlated with the Fugl-Meyer Assessment scores (hand+wrist) across all stroke patients. Conclusions Patterns in cortical connectivity may serve as a potential biomarker for the neural substratum associated with outcomes in hand function after subcortical stroke. PMID:23285171

  18. 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

  19. 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

  20. fMRI evidence of neural abnormalities in the subcortical face processing system in ASD

    PubMed Central

    Kleinhans, Natalia M.; Richards, Todd; Johnson, L. Clark; Weaver, Kurt E.; Greenson, Jessica; Dawson, Geraldine; Aylward, Elizabeth

    2012-01-01

    Recent evidence suggests that a rapid, automatic face-detection system is supported by subcortical structures including the amygdala, pulvinar, and superior colliculus. Early emerging abnormalities in these structures may be related to reduced social orienting in children with autism, and subsequently, to aberrant development of cortical circuits involved in face processing. Our objective was to determine whether functional abnormalities in the subcortical face processing system are present in adults with autism spectrum disorders (ASD) during supraliminal fearful face processing. Participants included twenty-eight individuals with ASD and 25 controls group-matched on age, IQ, and behavioral performance. The ASD group met diagnostic criteria on the ADI-R, ADOS-G, and DSM-IV. Both the ASD and control groups showed significant activation in bilateral fusiform gyri. The control group exhibited additional significant responses in the right amygdala, right pulvinar, and bilateral superior colliculi. In the direct group comparison, the controls showed significantly greater activation in the left amygdala, bilateral fusiform gyrus, right pulvinar, and bilateral superior colliculi. No brain region showed significantly greater activation in the ASD group compared to the controls. Thus, basic rapid face identification mechanisms appear to be functional in ASD. However, individuals with ASD failed to engage the subcortical brain regions involved in face detection and automatic emotional face processing, suggesting a core mechanism for impaired socioemotional processing in ASD. Neural abnormalities in this system may contribute to early emerging deficits in social orienting and attention, the putative precursors to abnormalities in social cognition and cortical face processing specialization. PMID:20656041

  1. 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

  2. Subcortical discrimination of unperceived objects during binocular rivalry.

    PubMed

    Pasley, Brian N; Mayes, Linda C; Schultz, Robert T

    2004-04-08

    Rapid identification of behaviorally relevant objects is important for survival. In humans, the neural computations for visually discriminating complex objects involve inferior temporal cortex (IT). However, less detailed but faster form processing may also occur in a phylogenetically older subcortical visual system that terminates in the amygdala. We used binocular rivalry to present stimuli without conscious awareness, thereby eliminating the IT object representation and isolating subcortical visual input to the amygdala. Functional magnetic resonance imaging revealed significant brain activation in the left amygdala but not in object-selective IT in response to unperceived fearful faces compared to unperceived nonface objects. These findings indicate that, for certain behaviorally relevant stimuli, a high-level cortical representation in IT is not required for object discrimination in the amygdala.

  3. 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.

  4. Utility of indocyanine green videoangiography in subcortical arteriovenous malformation resection.

    PubMed

    Rustemi, Oriela; Scienza, Renato; Della Puppa, Alessandro

    2017-07-01

    Subcortical arteriovenous malformations (AVMs) are surgically challenging. Localization is crucial for eloquent areas, and complete resection evaluation is uncertain. Indocyanine green videoangiography (ICG-VA) can assist this surgery. An illustrative video of a subcortical frontoparietal bleeding AVM resection assisted by ICG-VA is presented. A bleeding arterial feeder aneurysm was embolized in the acute phase to protect against rebleeding. ICG-VA helped to detect the AVM's superficial arterialized draining vein, distinguishing it from normal cortical veins. This enabled a customized sulcus approach. ICG-VA showed normalized flow through the previously arterialized vein, confirming the AVM's complete resection. This applies when there is a single drainage remaining. The video can be found here: https://youtu.be/L7yJEE66kV0 .

  5. 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.

  6. 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.

  7. Zfp312 is required for subcortical axonal projections and dendritic morphology of deep-layer pyramidal neurons of the cerebral cortex

    PubMed Central

    Chen, Jie-Guang; Rašin, Mladen-Roko; Kwan, Kenneth Y.; Šestan, Nenad

    2005-01-01

    Pyramidal neurons of the cerebral cortex display marked layer- and subtype-specific differences in their axonal projections and dendritic morphologies. Here we show that transcription factor Zfp312 is selectively expressed by layer V and VI subcortical projection pyramidal neurons and their progenitor cells. Knocking down Zfp312 with small interfering RNAs dramatically reduced the number of subcortical axonal projections from deep-layer pyramidal neurons and altered their dendritic morphology. In contrast, misexpression of Zfp312 in cortically projecting pyramidal neurons of layers II and III induced the expression of Tbr1, a transcription factor enriched in deep-layer neurons, and the formation of ectopic subcortical axonal projections. Thus, our results indicate that transcription factor Zfp312 plays a critical role in layer- and neuronal subtype-specific patterning of cortical axonal projections and dendritic morphologies. PMID:16314561

  8. Motor system activation after subcortical stroke depends on corticospinal system integrity

    PubMed Central

    Ward, Nick S.; Newton, Jennifer M.; Swayne, Orlando B. C.; Lee, Lucy; Thompson, Alan J.; Greenwood, Richard J.; Rothwell, John C.; Frackowiak, Richard S. J.

    2013-01-01

    Movement-related brain activation patterns after subcortical stroke are characterized by relative overactivations in cortical motor areas compared with controls. In patients able to perform a motor task, overactivations are greater in those with more motor impairment. We hypothesized that recruitment of motor regions would shift from primary to secondary motor networks in response to impaired functional integrity of the corticospinal system (CSS). We measured the magnitude of brain activation using functional MRI during a motor task in eight chronic subcortical stroke patients. CSS functional integrity was assessed using transcranial magnetic stimulation to obtain stimulus/response curves for the affected first dorsal interosseus muscle, with a shallower gradient representing increasing disruption of CSS functional integrity. A negative correlation between the gradient of stimulus/response curve and magnitude of task-related brain activation was found in several motor-related regions, including ipsilesional posterior primary motor cortex [Brodmann area (BA) 4p], contralesional anterior primary motor cortex (BA 4a), bilateral premotor cortex, supplementary motor area, intraparietal sulcus, dorsolateral prefrontal cortex and contralesional superior cingulate sulcus. There were no significant positive correlations in any brain region. These results suggest that impaired functional integrity of the CSS is associated with recruitment of secondary motor networks in both hemispheres in an attempt to generate motor output to spinal cord motoneurons. Secondary motor regions are less efficient at generating motor output so this reorganization can only be considered partially successful in reducing motor impairment after stroke. PMID:16421171

  9. 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.

  10. Methylphenidate and Atomoxetine Inhibit Social Play Behavior through Prefrontal and Subcortical Limbic Mechanisms in Rats

    PubMed Central

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

    2015-01-01

    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. PMID:25568111

  11. 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

  12. 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

  13. 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...

  14. 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...

  15. 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.

  16. Structural damage and functional reorganization in ipsilesional m1 in well-recovered patients with subcortical stroke.

    PubMed

    Zhang, Jing; Meng, Liangliang; Qin, Wen; Liu, Ningning; Shi, Fu-Dong; Yu, Chunshui

    2014-03-01

    Both structural atrophy and functional reorganization of the primary motor cortex (M1) have been reported in patients with subcortical infarctions affecting the motor pathway. However, the relationship between structural impairment and functional reorganization in M1 remains unclear. Twenty-six patients exhibiting significant recovery after subcortical infarctions were investigated using multimodal MRI techniques. Structural impairment was assessed via cortical thickness, and functional reorganization was analyzed using task-evoked activation, amplitude of low-frequency fluctuation, and resting-state functional connectivity. Compared with healthy controls, patients with stroke exhibited reduced cortical thickness in the ipsilesional M1; however, this region exhibited increased task-evoked activation, amplitude of low-frequency fluctuation, and resting-state functional connectivity in these patients. Patients with stroke demonstrated increased task-evoked activation in another ipsilesional M1 region, in which increased amplitude of low-frequency fluctuation and resting-state functional connectivity were observed. The structural and functional changes in M1 were located selectively in the ipsilesional hemisphere. We provide convincing evidence that indicates extensive functional reorganization in the ipsilesional M1 of patients with chronic subcortical infarctions, including the structurally impaired M1 region.

  17. Children with Epilepsy and Anxiety: Subcortical and Cortical Differences

    PubMed Central

    Jones, Jana E.; Jackson, Daren C.; Chambers, Karlee L.; Dabbs, Kevin; Hsu, David A.; Stafstrom, Carl E.; Seidenberg, Michael; Hermann, Bruce P.

    2014-01-01

    Summary Objective Using a hypothesis driven approach, subcortical and cortical regions implicated in anxiety disorders in the general population were examined in children with recent-onset epilepsy with versus without anxiety compared to controls. This study reports frequency of anxiety disorders while examining familial, clinical and demographic variables associated with anxiety in children with epilepsy. Method Participants included 88 children with epilepsy aged 8–18 years; 25 with a current anxiety disorder and 63 children with epilepsy no current anxiety disorder. 49 controls without anxiety disorders were included. T1 volumetric MRI scans were collected; subcortical volumes and cortical thickness were computed using the FreeSurfer image analysis suite. Analyses focused on adjusted measures of subcortical volumes and cortical thickness. Results Relative to controls, larger left amygdala volumes were found in the Epilepsy Anxiety group compared to the Epilepsy No Anxiety group (p = 0.027). In the hippocampus there were no significant differences between groups. Examination of cortical thickness demonstrated that the Epilepsy Anxiety group showed thinning in left medial orbitofrontal (p=0.001), right lateral orbitofrontal (p=0.017), and right frontal pole (p=0.009). There were no differences between groups in age, sex, IQ, age of onset, medications, or duration of epilepsy. There were more family members with a history of anxiety disorders in the Epilepsy Anxiety group compared to the Epilepsy No Anxiety group (p=0.005). Significance Anxiety is a common psychiatric comorbidity in children with recent-onset epilepsy with volumetric enlargement of the amygdala and thinner cortex in orbital and other regions of prefrontal cortex, suggesting structural abnormalities in brain regions that are part of the dysfunctional networks reported in individuals with anxiety disorders in the general population. These findings are evident early in the course of epilepsy, are

  18. 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.

  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. 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.

  1. 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

  2. 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

  3. 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.

  4. 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

  5. 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

  6. Subcortical Projections of Area V2 in the Macaque

    PubMed Central

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

    2015-01-01

    To investigate the subcortical efferent connections of visual area V2, we injected tritiated amino acids under electrophysiological control into 15 V2 sites in 14 macaques. The injection sites included the fovea representation as well as representations ranging from central to far peripheral eccentricities in both the upper and lower visual fields. The results indicated that V2 projects topographically to different portions of the inferior and lateral pulvinar and to the superficial and intermediate layers of the superior colliculus. Within the pulvinar, the V2 projections terminated in fields P1, P2, and P4, with the strongest projection being in P2. Central visual field injections in V2 labeled projection zones in P1 and P2, whereas peripheral field injections labeled P1, P2, and P4. No projections were found in P3. Both central and peripheral field injections in V2 projected topographically to the superficial and intermediate layers of the superior colliculus. Projections from V2 to the pulvinar and the superior colliculus constituted cortical–subcortical loops through which circuits serving spatial attention are activated. PMID:24456395

  7. 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.

  8. Cytokine Effects on the Basal Ganglia and Dopamine Function: the Subcortical Source of Inflammatory Malaise

    PubMed Central

    Felger, Jennifer C.; Miller, Andrew H.

    2012-01-01

    Data suggest that cytokines released during the inflammatory response target subcortical structures including the basal ganglia as well as dopamine function to acutely induce behavioral changes that support fighting infection and wound healing. However, chronic inflammation and exposure to inflammatory cytokines appears to lead to persisting alterations in the basal ganglia and dopamine function reflected by anhedonia, fatigue, and psychomotor slowing. Moreover, reduced neural responses to hedonic reward, decreased dopamine metabolites in the cerebrospinal fluid and increased presynaptic dopamine uptake and decreased turnover have been described. This multiplicity of changes in the basal ganglia and dopamine function suggest fundamental effects of inflammatory cytokines on dopamine synthesis, packaging, release and/or reuptake, which may sabotage and circumvent the efficacy of current treatment approaches. Thus, examination of the mechanisms by which cytokines alter the basal ganglia and dopamine function will yield novel insights into the treatment of cytokine-induced behavioral changes and inflammatory malaise. PMID:23000204

  9. Cytokine effects on the basal ganglia and dopamine function: the subcortical source of inflammatory malaise.

    PubMed

    Felger, Jennifer C; Miller, Andrew H

    2012-08-01

    Data suggest that cytokines released during the inflammatory response target subcortical structures including the basal ganglia as well as dopamine function to acutely induce behavioral changes that support fighting infection and wound healing. However, chronic inflammation and exposure to inflammatory cytokines appears to lead to persisting alterations in the basal ganglia and dopamine function reflected by anhedonia, fatigue, and psychomotor slowing. Moreover, reduced neural responses to hedonic reward, decreased dopamine metabolites in the cerebrospinal fluid and increased presynaptic dopamine uptake and decreased turnover have been described. This multiplicity of changes in the basal ganglia and dopamine function suggest fundamental effects of inflammatory cytokines on dopamine synthesis, packaging, release and/or reuptake, which may sabotage and circumvent the efficacy of current treatment approaches. Thus, examination of the mechanisms by which cytokines alter the basal ganglia and dopamine function will yield novel insights into the treatment of cytokine-induced behavioral changes and inflammatory malaise. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. Independent cognitive effects of atrophy and diffuse subcortical and thalamico-cortical cerebrovascular disease in dementia.

    PubMed

    Swartz, Richard H; Stuss, Donald T; Gao, Fuqiang; Black, Sandra E

    2008-03-01

    Brain atrophy, cortical infarction, and subcortical ischemic vasculopathy have all been associated with cognitive dysfunction. The interrelationships between these pathologies and their independent contributions to cognitive function remain unclear. Despite the high frequency of Alzheimer disease (AD) in those with clinically diagnosed vascular dementia, and the frequent findings of vascular disease in those with clinically diagnosed AD, many studies of brain-behavior relationships in dementia consider these populations separately. The present study sought to identify the correlates of independent domains of cognitive impairment in an unselected sample across a large range of severity and overlap of AD and VaD. Two hundred five individuals from the Sunnybrook Dementia Study recruited from a university Memory clinic had detailed neuropsychological testing and MRI quantification using a multi-step postprocessing algorithm. A factor analysis of the cognitive protocol yielded a 3-factor solution, provisionally labeled: (1) short-term memory and language, (2) attention and working memory, and (3) mental flexibility. A factor analysis of brain measures identified 3 independent factors with measures of (1) brain atrophy, (2) subcortical vascular disease, and (3) strategic infarcts (anterior-medial thalamus and cortical infarcts). After accounting for the effects of age and education, measures of brain atrophy were the strongest correlates of all cognitive domains. Small vessel disease was independently associated with general severity, impaired short-term memory/language, and reduced mental flexibility, but not with poor working memory, presumably through disruption of frontal-subcortical connections. In contrast, strategic infarcts to anterior-medial thalamus and cortical gray matter were associated with poor short-term and working memory, but not with impairments in mental flexibility or global severity measures. These data support the hypothesis that the thalamico

  11. 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.…

  12. 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.…

  13. [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.

  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. 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.

  16. Functional MRI of the immediate impact of transcranial magnetic stimulation on cortical and subcortical motor circuits.

    PubMed

    Bestmann, Sven; Baudewig, Jürgen; Siebner, Hartwig R; Rothwell, John C; Frahm, Jens

    2004-04-01

    Recent studies indicate that the cortical effects of transcranial magnetic stimulation (TMS) may not be localized to the site of stimulation, but spread to other distant areas. Using echo-planar imaging with blood-oxygenation-level-dependent (BOLD) contrast at 3 Tesla, we measured MRI signal changes in cortical and subcortical motor regions during high-frequency (3.125 Hz) repetitive TMS (rTMS) of the left sensorimotor cortex (M1/S1) at intensities above and below the active motor threshold in healthy humans. The supra- and subthreshold nature of the TMS pulses was confirmed by simultaneous electromyographic monitoring of a hand muscle. Suprathreshold rTMS activated a network of primary and secondary cortical motor regions including M1/S1, supplementary motor area, dorsal premotor cortex, cingulate motor area, the putamen and thalamus. Subthreshold rTMS elicited no MRI-detectable activity in the stimulated M1/S1, but otherwise led to a similar activation pattern as obtained for suprathreshold stimulation though at reduced intensity. In addition, we observed activations within the auditory system, including the transverse and superior temporal gyrus, inferior colliculus and medial geniculate nucleus. The present findings support the notion that re-afferent feedback from evoked movements represents the dominant input to the motor system via M1 during suprathreshold stimulation. The BOLD MRI changes in motor areas distant from the site of subthreshold stimulation are likely to originate from altered synaptic transmissions due to induced excitability changes in M1/S1. They reflect the capability of rTMS to target both local and remote brain regions as tightly connected constituents of a cortical and subcortical network.

  17. 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. Copyright © 2015 the authors 0270-6474/15/350161-09$15.00/0.

  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. Intraoperative subcortical stimulation mapping for hemispherical perirolandic gliomas located within or adjacent to the descending motor pathways: evaluation of morbidity and assessment of functional outcome in 294 patients.

    PubMed

    Keles, G Evren; Lundin, David A; Lamborn, Kathleen R; Chang, Edward F; Ojemann, George; Berger, Mitchel S

    2004-03-01

    Intraoperative stimulation mapping of subcortical white matter tracts during the resection of gliomas has become a valuable surgical adjunct that is used to reduce morbidity associated with tumor removal. The purpose of this retrospective analysis was to assess the morbidity and functional outcome associated with this method, thus allowing the surgeon to predict the likelihood of causing a temporary or permanent motor deficit. In this study, the authors report their experience with intraoperative stimulation mapping to locate subcortical motor pathways in 294 patients who underwent surgery for hemispheric gliomas within or adjacent to the rolandic cortex. Data were collected regarding intraoperative cortical and subcortical stimulation mapping results, along with the patient's neurological status pre- and postoperatively. For patients in whom an additional motor deficit occurred postoperatively, its evolution was examined. Of 294 patients, an additional postoperative motor deficit occurred in 60 (20.4%). Of those 60, 23 (38%) recovered to their preoperative baseline status within the 1st postoperative week. Another 12 (20%) recovered from their postoperative motor deficit by the end of the 4th postoperative week, and 11 more recovered to their baseline status by the end of the 3rd postoperative month. Thus, 46 (76.7%) of 60 patients with postoperative motor deficits regained their baseline function within the first 90 days after surgery. The remaining 14 patients (4.8% of the entire study population of 294) had a persistent motor deficit after 3 months. Patients whose subcortical pathways were identified with stimulation mapping were more prone to develop an additional (temporary or permanent) motor deficit than those in whom subcortical pathways could not be identified (27.5% compared with 13.1%, p = 0.003). This was also true when additional (permanent) motor deficits lasted more than 3 months (7.4% when subcortical pathways were found, compared with 2.1% when

  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 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.

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

    PubMed

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

    1986-03-01

    We examined 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. At a concentration that completely inhibited PMN chemotaxis, WGA-D had no effect on either the uptake or release of [3H]-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 microM FMLP for 10 min at 4 degrees 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 [125I]-WGA-D demonstrated that PMN did not internalize WGA-D spontaneously. PMN did internalize [125I]-WGA-D, however, when stimulated with FMLP. Internalization of WGA-D by FMLP-stimulated PMN was rapid, dependent on the concentration of FMLP, and specific. Internalization of [125I]-WGA-D by PMN did not occur when highly purified human C5a, instead of FMLP, was used as a stimulus. Subcellular fractionation studies demonstrated that [125I]-WGA-D and [3H]-FMLP were co-internalized by PMN, and segregated to a compartment co-migrating with Golgi markers. Western blot analysis, using PMN plasma membranes, demonstrated that WGA-D bound to a single membrane glycoprotein that migrated with an apparent m.w. of 62,000. The data indicate that WGA-D, perhaps by binding to the FMLP receptor, inhibits FMLP-induced PMN chemotaxis by blocking

  5. 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

  6. 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

  7. Autologous chondrocyte implantation. Culture in a TGF-beta-containing medium enhances the re-expression of a chondrocytic phenotype in passaged human chondrocytes in pellet culture.

    PubMed

    Goldberg, A J; Lee, D A; Bader, D L; Bentley, G

    2005-01-01

    An increasing number of patients are treated by autologous chondrocyte implantation (ACI). This study tests the hypothesis that culture within a defined chondrogenic medium containing TGF-beta enhances the re-expression of a chondrocytic phenotype and the subsequent production of cartilaginous extracellular matrix by human chondrocytes used in ACI. Chondrocytes surplus to clinical requirements for ACI from 24 patients were pelleted and cultured in either DMEM (Dulbecco's modified eagles medium)/ITS+Premix/TGF-beta1 or DMEM/10%FCS (fetal calf serum) and were subsequently analysed biochemically and morphologically. Pellets cultured in DMEM/ITS+/TGF-beta1 stained positively for type-II collagen, while those maintained in DMEM/10%FCS expressed type-I collagen. The pellets cultured in DMEM/ITS+/TGF-beta1 were larger and contained significantly greater amounts of DNA and glycosaminoglycans. This study suggests that the use of a defined medium containing TGF-beta is necessary to induce the re-expression of a differentiated chondrocytic phenotype and the subsequent stimulation of glycosaminoglycan and type-II collagen production by human monolayer expanded chondrocytes.

  8. 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. © 2013. Published by Elsevier Inc. All rights reserved.

  9. 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

  10. Machine learning in a graph framework for subcortical segmentation

    NASA Astrophysics Data System (ADS)

    Guo, Zhihui; Kashyap, Satyananda; Sonka, Milan; Oguz, Ipek

    2017-02-01

    Automated and reliable segmentation of subcortical structures from human brain magnetic resonance images is of great importance for volumetric and shape analyses in quantitative neuroimaging studies. However, poor boundary contrast and variable shape of these structures make the automated segmentation a tough task. We propose a 3D graph-based machine learning method, called LOGISMOS-RF, to segment the caudate and the putamen from brain MRI scans in a robust and accurate way. An atlas-based tissue classification and bias-field correction method is applied to the images to generate an initial segmentation for each structure. Then a 3D graph framework is utilized to construct a geometric graph for each initial segmentation. A locally trained random forest classifier is used to assign a cost to each graph node. The max-flow algorithm is applied to solve the segmentation problem. Evaluation was performed on a dataset of T1-weighted MRI's of 62 subjects, with 42 images used for training and 20 images for testing. For comparison, FreeSurfer, FSL and BRAINSCut approaches were also evaluated using the same dataset. Dice overlap coefficients and surface-to-surfaces distances between the automated segmentation and expert manual segmentations indicate the results of our method are statistically significantly more accurate than the three other methods, for both the caudate (Dice: 0.89 +/- 0.03) and the putamen (0.89 +/- 0.03).

  11. 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.

  12. Intrinsic Regression Models for Medial Representation of Subcortical Structures

    PubMed Central

    Shi, Xiaoyan; Zhu, Hongtu; Ibrahim, Joseph G.; Liang, Faming; Lieberman, Jeffrey; Styner, Martin

    2011-01-01

    The aim of this paper is to develop a semiparametric model for describing the variability of the medial representation of subcortical structures, which belongs to a Riemannian manifold, and establishing its association with covariates of interest, such as diagnostic status, age and gender. We develop a two-stage estimation procedure to calculate the parameter estimates. The first stage is to calculate an intrinsic least squares estimator of the parameter vector using the annealing evolutionary stochastic approximation Monte Carlo algorithm and then the second stage is to construct a set of estimating equations to obtain a more efficient estimate with the intrinsic least squares estimate as the starting point. We use Wald statistics to test linear hypotheses of unknown parameters and establish their limiting distributions. Simulation studies are used to evaluate the accuracy of our parameter estimates and the finite sample performance of the Wald statistics. We apply our methods to the detection of the difference in the morphological changes of the left and right hippocampi between schizophrenia patients and healthy controls using medial shape description. PMID:23794769

  13. Machine learning in a graph framework for subcortical segmentation

    PubMed Central

    Guo, Zhihui; Kashyap, Satyananda; Sonka, Milan; Oguz, Ipek

    2017-01-01

    Automated and reliable segmentation of subcortical structures from human brain magnetic resonance images is of great importance for volumetric and shape analyses in quantitative neuroimaging studies. However, poor boundary contrast and variable shape of these structures make the automated segmentation a tough task. We propose a 3D graph-based machine learning method, called LOGISMOS-RF, to segment the caudate and the putamen from brain MRI scans in a robust and accurate way. An atlas-based tissue classification and bias-field correction method is applied to the images to generate an initial segmentation for each structure. Then a 3D graph framework is utilized to construct a geometric graph for each initial segmentation. A locally trained random forest classifier is used to assign a cost to each graph node. The max-flow algorithm is applied to solve the segmentation problem. Evaluation was performed on a dataset of T1-weighted MRI’s of 62 subjects, with 42 images used for training and 20 images for testing. For comparison, FreeSurfer and FSL approaches were also evaluated using the same dataset. Dice overlap coefficients and surface-to-surfaces distances between the automated segmentation and expert manual segmentations indicate the results of our method are statistically significantly more accurate than the other two methods, for both the caudate (Dice: 0.89 ± 0.03) and the putamen (0.89 ± 0.03). PMID:28626291

  14. 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

  15. 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...

  16. 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...

  17. 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

  18. Involvement of the Serotonin Transporter Gene in Accurate Subcortical Speech Encoding.

    PubMed

    Selinger, Lenka; Zarnowiec, Katarzyna; Via, Marc; Clemente, Immaculada C; Escera, Carles

    2016-10-19

    A flourishing line of evidence has highlighted the encoding of speech sounds in the subcortical auditory system as being shaped by acoustic, linguistic, and musical experience and training. And while the heritability of auditory speech as well as nonspeech processing has been suggested, the genetic determinants of subcortical speech processing have not yet been uncovered. Here, we postulated that the serotonin transporter-linked polymorphic region (5-HTTLPR), a common functional polymorphism located in the promoter region of the serotonin transporter gene (SLC6A4), is implicated in speech encoding in the human subcortical auditory pathway. Serotonin has been shown as essential for modulating the brain response to sound both cortically and subcortically, yet the genetic factors regulating this modulation regarding speech sounds have not been disclosed. We recorded the frequency following response, a biomarker of the neural tracking of speech sounds in the subcortical auditory pathway, and cortical evoked potentials in 58 participants elicited to the syllable /ba/, which was presented >2000 times. Participants with low serotonin transporter expression had higher signal-to-noise ratios as well as a higher pitch strength representation of the periodic part of the syllable than participants with medium to high expression, possibly by tuning synaptic activity to the stimulus features and hence a more efficient suppression of noise. These results imply the 5-HTTLPR in subcortical auditory speech encoding and add an important, genetically determined layer to the factors shaping the human subcortical response to speech sounds. The accurate encoding of speech sounds in the subcortical auditory nervous system is of paramount relevance for human communication, and it has been shown to be altered in different disorders of speech and auditory processing. Importantly, this encoding is plastic and can therefore be enhanced by language and music experience. Whether genetic factors

  19. 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.

  20. 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.

  1. 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

  2. Neurodevelopmental outcome after severe traumatic brain injury in very young children: role for subcortical lesions.

    PubMed

    Bonnier, Christine; Marique, Patricia; Van Hout, Anne; Potelle, Dominique

    2007-05-01

    Traumatic brain injury is a major cause of mortality and morbidity in children younger than 15 years of age. To evaluate the role of subcortical lesions on neurodevelopmental outcomes, long-term outcomes of 50 children with severe traumatic brain injury before 4 years of age (accidental injury, n = 21, nonaccidental injury, n = 29) were reviewed retrospectively and compared with late magnetic resonance imaging (MRI) findings: no visible lesions, cortical lesions, or subcortical lesions. Subcortical lesions occurred in both accidental and nonaccidental traumatic brain injuries. Traumatic brain injury severity (initial Glasgow Coma Scale or coma duration) was significantly associated with subcortical lesions. Long-term motor or visual deficiencies occurred in one third of patients and cognitive deficiencies in 52.1%. Although deficiencies occurred without visible MRI lesions, global outcome scores, motor delay, visual impairment, head growth slowing, global intellectual quotients, and planning performances were significantly worse in patients with subcortical lesions. An alarming deterioration in intellectual quotient over time was noted. It was concluded that neurodevelopmental outcomes are worrisome after severe traumatic brain injury in young children, and subcortical lesions affect the prognosis.

  3. 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

  4. 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

  5. Stimulus rate and subcortical auditory processing of speech.

    PubMed

    Krizman, Jennifer L; Skoe, Erika; Kraus, Nina

    2010-01-01

    Many sounds in the environment, including speech, are temporally dynamic. The auditory brainstem is exquisitely sensitive to temporal features of the incoming acoustic stream, and by varying the speed of presentation of these auditory signals it is possible to investigate the precision with which temporal cues are represented at a subcortical level. Therefore, to determine the effects of stimulation rate on the auditory brainstem response (ABR), we recorded evoked responses to both a click and a consonant-vowel speech syllable (/da/) presented at three rates (15.4, 10.9 and 6.9 Hz). We hypothesized that stimulus rate affects the onset to speech-evoked responses to a greater extent than click-evoked responses and that subcomponents of the speech- ABR are distinctively affected. While the click response was invariant with changes in stimulus rate, timing of the onset response to /da/ varied systematically, increasing in peak latency as presentation rate increased. Contrasts between the click- and speech-evoked onset responses likely reflect acoustic differences, where the speech stimulus onset is more gradual, has more delineated spectral information, and is more susceptible to backward masking by the subsequent formant transition. The frequency-following response (FFR) was also rate dependent, with response magnitude of the higher frequencies (>400 Hz), but not the frequencies corresponding to the fundamental frequency, diminishing with increasing rate. The selective impact of rate on high-frequency components of the FFR implicates the involvement of distinct underlying neural mechanisms for high- versus low-frequency components of the response. Furthermore, the different rate sensitivities of the speech-evoked onset response and subcomponents of the FFR support the involvement of different neural streams for these two responses. Taken together, these differential effects of rate on the ABR components likely reflect distinct aspects of auditory function such that

  6. Stimulus Rate and Subcortical Auditory Processing of Speech

    PubMed Central

    Krizman, Jennifer; Skoe, Erika; Kraus, Nina

    2010-01-01

    Many sounds in the environment, including speech, are temporally dynamic. The auditory brainstem is exquisitely sensitive to temporal features of the incoming acoustic stream, and by varying the speed of presentation of these auditory signals it is possible to investigate the precision with which temporal cues are represented at a subcortical level. Therefore, to determine the effects of stimulation rate on the auditory brainstem response (ABR), we recorded evoked responses to both a click and a consonant-vowel speech syllable (/da/) presented at three rates (15.4, 10.9 and 6.9 Hz). We hypothesized that stimulus rate affects the onset to speech-evoked responses to a greater extent than click-evoked responses and that subcomponents of the speech-ABR are distinctively affected. While the click response was invariant with changes in stimulus rate, timing of the onset response to /da/ varied systematically, increasing in peak latency as presentation rate increased. Contrasts between the click- and speech-evoked onset responses likely reflect acoustic differences, where the speech stimulus onset is more gradual, has more delineated spectral information, and is more susceptible to backward masking by the subsequent formant transition. The frequency-following response (FFR) was also rate dependent, with response magnitude of the higher frequencies (>400 Hz), but not the frequencies corresponding to the fundamental frequency, diminishing with increasing rate. The selective impact of rate on high-frequency components of the FFR implicates the involvement of distinct underlying neural mechanisms for high- versus low-frequency components of the response. Furthermore, the different rate sensitivities of the speech-evoked onset response and subcomponents of the FFR support the involvement of different neural streams for these two responses. Taken together, these differential effects of rate on the ABR components likely reflect distinct aspects of auditory function such that

  7. 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

  8. 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

  9. 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.

  10. 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

  11. 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.

  12. 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.

  13. 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

  14. Regional Cortical Thickness and Subcortical Volume Changes Are Associated with Cognitive Impairments in the Drug-Naive Patients with Late-Onset Depression

    PubMed Central

    Lim, Hyun Kook; Jung, Won Sang; Ahn, Kook Jin; Won, Wang Youn; Hahn, Changtae; Lee, Seung Yup; Kim, InSeong; Lee, Chang Uk

    2012-01-01

    Previous studies have shown an association between late-onset depression (LOD) and cognitive impairment in older adults. However, the neural correlates of this relationship are not yet clear. The aim of this study was to investigate the differences in both cortical thickness and subcortical volumes between drug-naive LOD patients and healthy controls and explore the relationship between LOD and cognitive impairments. A total of 48 elderly, drug-naive patients with LOD and 47 group-matched healthy control subjects underwent 3T MRI scanning, and the cortical thickness was compared between the groups in multiple locations, across the continuous cortical surface. The subcortical volumes were also compared on a structure-by-structure basis. Subjects with LOD exhibited significantly decreased cortical thickness in the rostral anterior cingulate cortex, the medial orbitofrontal cortex, dorsolateral prefrontal cortex, the superior and middle temporal cortex, and the posterior cingulate cortex when compared with healthy subjects (all p<0.05, false discovery rate corrected). Reduced volumes of the right hippocampus was also observed in LOD patients when compared with healthy controls (p<0.001). There were significant correlations between memory functions and cortical thickness of medial temporal, isthmus cingulate, and precuneus (p<0.001). This study was the first study to explore the relationships between the cortical thickness/subcortical volumes and cognitive impairments of drug-naive patients with LOD. These structural changes might explain the neurobiological mechanism of LOD as a risk factor of dementia. PMID:22048467

  15. 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

  16. 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.

  17. 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

  18. Cortical thickness, cortical and subcortical volume, and white matter integrity in patients with their first episode of major depression.

    PubMed

    Han, Kyu-Man; Choi, Sunyoung; Jung, Jeyoung; Na, Kyoung-Sae; Yoon, Ho-Kyoung; Lee, Min-Soo; Ham, Byung-Joo

    2014-02-01

    The uncertainty over the true morphological changes in brains with major depressive disorder (MDD) underlines the necessity of comprehensive studies with multimodal structural brain imaging analyses. This study aimed to evaluate the differences in cortical thickness, cortical and subcortical volume, and white matter integrity between first episode, medication-naïve MDD patients and healthy controls. Subjects with their first episode of MDD whose illness duration had not exceeded 6 months (n=20) were enrolled in this study and were compared to age-, sex-, and education level-matched healthy controls (n=22). All participants were subjected to T1-weighted structural magnetic resonance imaging (MRI). We used an automated procedure of FreeSurfer and Tract-based spatial statistics (TBSS) to analyze differences in cortical thickness, cortical and subcortical volume, and white matter integrity between two groups. The patients with first episode MDD exhibited significantly reduced cortical volume in the caudal anterior cingulate gyrus (P<0.0015) compared to healthy controls. We also observed altered white matter integrity in the body of the corpus callosum (P<0.01), reduced cortical volume of the caudal middle frontal gyrus and medial orbitofrontal gyrus, and enlarged hippocampal volume in the first episode MDD patients. We relied on a relatively small sample size and cortical volume reduction in several brain regions was not replicated in the analysis of cortical thickness. Using multimodal imaging analyses on medication-naïve first episode MDD patients, we demonstrated fundamental structural alteration of brain gray and white matter, such as reduced cortical volume of the caudal ACC and white matter integrity in the body of the corpus callosum. © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

  19. 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

  20. 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

  1. 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.

  2. 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.

  3. Reduced cortical and subcortical volumes in female adolescents with borderline personality disorder.

    PubMed

    Richter, Julia; Brunner, Romuald; Parzer, Peter; Resch, Franz; Stieltjes, Bram; Henze, Romy

    2014-03-30

    Volumetric alterations in limbic structures have been detected in adults, but not in adolescents with borderline personality disorder (BPD). We examined adolescents in the early stages of BPD to provide a unique opportunity to investigate which parts of the brain are initially affected by the disorder before confounding factors such as long-term medication or chronicity can mask them. A group of 60 right-handed female adolescents between 14 and 18 years of age (20 patients with BPD, 20 clinical controls, and 20 healthy controls) underwent magnetic resonance imaging (MRI). Focus was on the examination of hippocampal and amygdalar volume differences. Furthermore, a cortical thickness analysis was conducted. FreeSurfer software detected significant group differences in the right and left hippocampus and in the right amygdala. Additionally, significant volume reductions in frontal (right middle frontal gyrus, orbital part of the inferior frontal gyrus bilaterally), and parietal regions (superior parietal gyrus bilaterally) were found in adolescents with BPD compared with controls. No group differences in cortical thickness were revealed. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  4. 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. Copyright © 2016 the authors 0270-6474/16/362438-11$15.00/0.

  5. 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

  6. Application of semiochemicals to assess the biodiversity of subcortical insects following an ecosystem disturbance in a sub-boreal forest.

    PubMed

    Gandhi, Kamal J K; Gilmore, Daniel W; Haack, Robert A; Katovich, Steven A; Krauth, Steven J; Mattson, William J; Zasada, John C; Seybold, Steven J

    2009-12-01

    From 2000 through 2003 we used semiochemical-baited traps in northeastern Minnesota, USA, to assess changes in assemblages of subcortical forest insects after a catastrophic wind storm in 1999 and subsequent (1999-2000) fuel-reduction activities (salvage-logging and prescribed-burning). We determined the regional efficacy of fifteen semiochemical blends (pheromones and kairomones) as attractants for target and non-target subcortical insect species (Coleoptera: Anthribidae, Buprestidae, Cerambycidae, Cleridae, Cucujidae, Curculionidae, Histeridae, Nemonychidae, Salpingidae, Scolytidae, Tenebrionidae, and Hymenoptera: Siricidae). During the four summers, we trapped 86,471 subcortical insects (143 species) in baited and unbaited Lindgren funnel traps, and 500 beetles (44 species) in baited and unbaited pitfall traps. We report 23 new state collection records of subcortical insects from Minnesota. Trap catches of subcortical insects were greatest in the wind-disturbed areas 2 years after the event, and declined thereafter. Similar trends were observed for subcortical insects in the burned areas. Both wind-disturbance and burning increased the subcortical insect species richness and diversity on the landscape. The subcortical insect species compositions of the salvaged and burned forest areas differed from those of the undisturbed and wind-disturbed areas. Trap catches of subcortical insects in response to semiochemical treatments also varied with year of sampling and land-area treatment. The greatest diversity of subcortical beetle species was in traps baited with attractants for the scolytids, Dendroctonus valens [(+)-α-pinene and (−)-β-pinene] and Dryocoetes spp. [exo-brevicomin and (−)-α-pinene], perhaps reflecting the generic nature of the baits. The most distinct species compositions were collected in response to the woodborer and Dendroctonus simplex baits, whereas the species compositions in traps with the D. valens and Dryocoetes spp. baits, and the

  7. 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.

  8. 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.

  9. 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

  10. Cortical and subcortical motor mapping in rolandic and perirolandic glioma surgery: impact on postoperative morbidity and extent of resection.

    PubMed

    Carrabba, G; Fava, E; Giussani, C; Acerbi, F; Portaluri, F; Songa, V; Stocchetti, N; Branca, V; Gaini, S M; Bello, L

    2007-06-01

    Surgery for gliomas located inside or in proximity of motor cortex or tracts requires cortical and subcortical mapping to locate motor function; direct electrical stimulation of brain cortex or subcortical pathways allows identification and preservation of motor function. In this study we evaluated the effect which subcortical motor mapping had on postoperative morbidity and extent of resection in a series of patients with gliomas involving motor areas or pathways. One hundred and forty-six patients were included in the study. Intraoperative findings of primary motor cortex or subcortical tracts were reported, together with incidence of new postoperative deficits at short (1 week) and long term (1 month) examination. The relationship between intraoperative identification of subcortical motor tracts and extent of resection was reported. The motor strip was found in 133 patients (91%) and subcortical motor tracts in 91 patients (62.3%). New immediate postoperative motor deficits were documented in 59.3% of patients in whom a subcortical motor tract was identified intra-operatively and in 10.9% of those in whom subcortical tracts were not observed; permanent deficits were observed in 6.5% and 3.5%, respectively. A total resection was achieved in 94.4% of patients with high-grade gliomas and in 46.1% of those with low-grade gliomas.

  11. Enhanced interhemispheric functional connectivity compensates for anatomical connection damages in subcortical stroke.

    PubMed

    Liu, Jingchun; Qin, Wen; Zhang, Jing; Zhang, Xuejun; Yu, Chunshui

    2015-04-01

    Motor recovery after stroke has been shown to be correlated with both the fractional anisotropy (FA) of the affected corticospinal tract (CST) and the interhemispheric resting-state functional connectivity (rsFC) of the primary motor cortex (M1). However, the role of the restoration or enhancement of the M1-M1 rsFC in motor recovery remains largely unknown. We aimed to clarify this issue by investigating the correlations between the M1-M1 rsFC and the integrity of the M1-M1 anatomic connection and the affected CST in chronic subcortical stroke patients with good motor outcomes. Twenty patients and 16 healthy controls underwent multimodal magnetic resonance imaging examinations. Diffusion tensor imaging was used to reconstruct the M1-M1 anatomic connection and bilateral CSTs. White matter integrity of these tracts was assessed using FA. Resting-state functional magnetic resonance imaging was used to calculate M1-M1 rsFC. Group differences in these measures were compared. Correlations between M1-M1 rsFC and FA of the M1-M1 anatomic connection and the affected CST were analyzed in patients with stroke. Compared with healthy controls, patients with stroke exhibited significantly reduced FA in the affected CST and the M1-M1 anatomic connection and a significantly increased M1-M1 rsFC. The FA values of the affected CST were positively correlated with the M1-M1 anatomic connection, and these FA values were negatively correlated with the M1-M1 rsFC in these patients. Our findings suggest that the M1-M1 anatomic connection impairment is secondary to CST damage, and the M1-M1 rsFC enhancement may reflect compensatory or reactive neural plasticity in stroke patients with CST impairment. © 2015 American Heart Association, Inc.

  12. Subcortical Volume Loss in the Thalamus, Putamen, and Pallidum, Induced by Traumatic Brain Injury, Is Associated With Motor Performance Deficits.

    PubMed

    Gooijers, Jolien; Chalavi, Sima; Beeckmans, Kurt; Michiels, Karla; Lafosse, Christophe; Sunaert, Stefan; Swinnen, Stephan P

    2016-08-01

    Traumatic brain injury (TBI) has been associated with altered microstructural organization of white matter (WM) and reduced gray matter (GM). Although disrupted WM organization has been linked to poorer motor performance, the predictive value of GM atrophy for motor impairments in TBI remains unclear. Here, we investigated TBI-induced GM volumetric abnormalities and uniquely examined their relationship with bimanual motor impairments. 22 moderate to severe TBI patients (mean age = 25.9 years, standard deviation [SD] = 4.9 years; time since injury = 4.7 years, SD = 3.7 years) and 27 age- and gender-matched controls (mean age = 23.4 years; SD = 3.8 years) completed bimanual tasks and a structural magnetic resonance imaging scan. Cortical and subcortical GM volumes were extracted and compared between groups using FreeSurfer. The association between bimanual performance and GM volumetric measures was investigated using partial correlations. Relative to controls, patients performed significantly poorer on the bimanual tasks and demonstrated significantly smaller total GM as well as overall and regional subcortical GM. However, the groups did not show significant differences in regional cortical GM volume. The majority of the results remained significant even after excluding TBI patients with focal lesions, suggesting that TBI-induced volume reductions were predominantly caused by diffuse injury. Importantly, atrophy of the thalamus, putamen, and pallidum correlated significantly with poorer bimanual performance within the TBI group. Our results reveal that GM atrophy is associated with motor impairments in TBI, providing new insights into the etiology of motor control impairments following brain trauma. © The Author(s) 2015.

  13. Temporal Lobe and Frontal-Subcortical Dissociations in Non-Demented Parkinson's Disease with Verbal Memory Impairment.

    PubMed

    Tanner, Jared J; Mareci, Thomas H; Okun, Michael S; Bowers, Dawn; Libon, David J; Price, Catherine C

    2015-01-01

    The current investigation examined verbal memory in idiopathic non-dementia Parkinson's disease and the significance of the left entorhinal cortex and left entorhinal-retrosplenial region connections (via temporal cingulum) on memory impairment in Parkinson's disease. Forty non-demented Parkinson's disease patients and forty non-Parkinson's disease controls completed two verbal memory tests--a wordlist measure (Philadelphia repeatable Verbal Memory Test) and a story measure (Logical Memory). All participants received T1-weighted and diffusion magnetic resonance imaging (3T; Siemens) sequences. Left entorhinal volume and left entorhinal-retrosplenial connectivity (temporal cingulum edge weight) were the primary imaging variables of interest with frontal lobe thickness and subcortical structure volumes as dissociating variables. Individuals with Parkinson's disease showed worse verbal memory, smaller entorhinal volumes, but did not differ in entorhinal-retrosplenial connectivity. For Parkinson's disease entorhinal-retrosplenial edge weight had the strongest associations with verbal memory. A subset of Parkinson's disease patients (23%) had deficits (z-scores < -1.5) across both memory measures. Relative to non-impaired Parkinson's peers, this memory-impaired group had smaller entorhinal volumes. Although entorhinal cortex volume was significantly reduced in Parkinson's disease patients relative to non-Parkinson's peers, only white matter connections associated with the entorhinal cortex were significantly associated with verbal memory performance in our sample. There was also no suggestion of contribution from frontal-subcortical gray or frontal white matter regions. These findings argue for additional investigation into medial temporal lobe gray and white matter connectivity for understanding memory in Parkinson's disease.

  14. Brain imaging evidence of early involvement of subcortical regions in familial and sporadic Alzheimer's disease.

    PubMed

    Tentolouris-Piperas, Vasileios; Ryan, Natalie S; Thomas, David L; Kinnunen, Kirsi M

    2017-01-15

    Recent brain imaging studies have found changes in subcortical regions in presymptomatic autosomal dominant Alzheimer's disease (ADAD). These regions are also affected in sporadic Alzheimer's disease (sAD), but whether such changes are seen in early-stage disease is still uncertain. In this review, we discuss imaging studies published in the past 12 years that have found evidence of subcortical involvement in early-stage ADAD and/or sAD. Several papers have reported amyloid deposition in the striatum of presymptomatic ADAD mutation carriers, prior to amyloid deposition elsewhere. Altered caudate volume has also been implicated in early-stage ADAD, but findings have been variable. Less is known about subcortical involvement in sAD: the thalamus and striatum have been found to be atrophied in symptomatic patients, but their involvement in the preclinical phase remains unclear, in part due to the difficulties of studying this stage in sporadic disease. Longitudinal imaging studies comparing ADAD mutation carriers with individuals at high-risk for sAD may be needed to elucidate the significance of subcortical involvement in different AD clinical stages. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Language disturbances after non-thalamic subcortical stroke: a review of the literature.

    PubMed

    Bouvier, Liziane; Groulx, Bertrand; Martel-Sauvageau, Vincent; Monetta, Laura

    2017-06-01

    Language disorders following subcortical non-thalamic stroke show great variability across literature and a well-defined profile in these aphasic disturbances is yet to be established. The lack of recent and consistent literature on the subject complicates the management of subcortical aphasia. The aim of this study is to review the literature describing oral language disturbances following subcortical non-thalamic stoke affecting the basal ganglia and the surrounding white matter. A review of the literature of three databases (PubMed, PsycNet and LLBA), identifying research articles from 1997 to 2015, was completed. The quality of the selected studies was assessed using the Checklist for the assessment of methodological quality. Twenty-two articles met criteria for review and oral language assessment data were extracted for 114 subjects. The results suggest a predominance of deficits in more complex and demanding language levels (ex. discourse, syntax) and in language production (vs comprehension). Rapid recovery is expected, especially for lexical-semantic and receptive deficits. These findings show the importance of a complete oral language evaluation after subcortical stoke and provide recent data relative to expected deficits and recovery to guide clinicians in the management of these patients. They also suggest that a descriptive approach of the deficits may be more efficient and accurate than the use of a traditional classification of aphasia.

  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. 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.

  18. 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…

  19. Apraxia in a patient with lesion located in right sub-cortical area. Analysis of errors.

    PubMed

    Mozaz, M; Marti, J F; Carrera, E; De la Puente, E

    1990-12-01

    This report describes a case of apraxia caused by a right sided sub-cortical lesion. Performance on test for apraxia was impaired. A new type of error which involved demonstrating the use of objects on one's own body is reported. Some theoretical interpretations of the findings are discussed.

  20. 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…

  1. 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

  2. Altered regional cortical thickness and subcortical volume in women with primary dysmenorrhoea.

    PubMed

    Liu, P; Yang, J; Wang, G; Liu, Y; Liu, X; Jin, L; Liang, F; Qin, W; Calhoun, V D

    2016-04-01

    There is emerging evidence that primary dysmenorrhoea (PDM) is associated with altered brain function and structure. However, few studies have investigated changes in regional cortical thickness and subcortical volumes in PDM patients. The purpose of this study was to characterize differences in both cortical thickness and subcortical volumes between PDM patients and healthy controls (HCs). T1-weighted magnetic resonance images were obtained from 44 PDM patients and 32 HCs matched for age and handedness. Cortical thickness was compared in multiple locations across the continuous cortical surface, and subcortical volumes were compared on a structure-by-structure basis. Correlation analysis was then used to evaluate relationships between the clinical symptoms and abnormal brain structure in PDM. PDM patients had significantly increased cortical thickness in the orbitofrontal cortex (OFC), insula (IN), primary/secondary sensory area (SI/SII), superior temporal cortex (STC), precuneus (pCUN) and posterior cingulate cortex (PCC). Meanwhile, significantly decreased subcortical volumes of the caudate, thalamus and amygdala were found in PDM patients. Moreover, there were significant positive correlations between the PDM-related duration and the OFC, SFC, STC and IN. The MPQ scores were positively correlated with the pCUN. These findings provide further evidence for grey matter changes in patients with PDM, and in addition, the results support relationships between the structural abnormalities and their role in symptom production. All these results are likely to be potential valuable to provide us with direct information about the neural basis of PDM. © 2015 European Pain Federation - EFIC®

  3. 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…

  4. 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…

  5. 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.

  6. The cortical and sub-cortical network of sensory evoked response in healthy subjects.

    PubMed

    Muthuraman, M; Hellriegel, H; Groppa, S; Deuschl, G; Raethjen, J

    2013-01-01

    The aim of this study was to find the cortical and sub-cortical network responsible for the sensory evoked coherence in healthy subjects during electrical stimulation of right median nerve at wrist. The multitaper method was used to estimate the power and coherence spectrum followed by the source analysis method dynamic imaging of coherent sources (DICS) to find the highest coherent source for the basic frequency 3 Hz and the complete cortical and sub-cortical network responsible for the sensory evoked coherence in healthy subjects. The highest coherent source for the basic frequency was in the posterior parietal cortex for all the subjects. The cortical and sub-cortical network comprised of the primary sensory motor cortex (SI), secondary sensory motor cortex (SII), frontal cortex and medial pulvinar nucleus in the thalamus. The cortical and sub-cortical network responsible for the sensory evoked coherence was found successfully with a 64-channel EEG system. The sensory evoked coherence is involved with a thalamo-cortical network in healthy subjects.

  7. 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

  8. 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

  9. Shape of the Central Sulcus and Disability After Subcortical Stroke: A Motor Reserve Hypothesis.

    PubMed

    Jouvent, Eric; Sun, Zhong Yi; De Guio, François; Duchesnay, Edouard; Duering, Marco; Ropele, Stefan; Dichgans, Martin; Mangin, Jean-François; Chabriat, Hugues

    2016-04-01

    Both brain and cognitive reserves modulate the clinical impact of chronic brain diseases. Whether a motor reserve also modulates the relationships between stroke and disability is unknown. We aimed to determine whether the shape of the central sulcus, a marker of the development of underlying motor connections, is independently associated with disability in patients with a positive history of small subcortical ischemic stroke. Shapes of central sulci were reconstructed from high-resolution magnetic resonance imaging and ordered without supervision according to a validated algorithm in 166 patients with a positive history of small subcortical ischemic stroke caused by CADASIL (Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy), a severe monogenic cerebral small vessel disease affecting young patients. Ordinal logistic regression modeling was used to test the relationships between modified Rankin scale, a disability scale strongly weighted toward motor disability, and sulcal shape. Modified Rankin scale was strongly associated with sulcal shape, independent of age, sex, and level of education (proportional odds ratio =1.19, 95% confidence interval =1.06-1.35; P=0.002). Results remained significant after further adjustment for brain atrophy, volume of lacunes, and volume of white matter hyperintensities of presumed vascular origin. The severity of disability in patients with a positive history of small subcortical ischemic stroke caused by a severe cerebral small vessel disease is related to the shape of the central sulcus, independently of the main determinants of disability. These results support the concept of a motor reserve that could modulate the clinical severity in patients with a positive history of small subcortical ischemic stroke. © 2016 American Heart Association, Inc.

  10. Continuous physical examination during subcortical resection in awake craniotomy patients: Its usefulness and surgical outcome.

    PubMed

    Bunyaratavej, Krishnapundha; Sangtongjaraskul, Sunisa; Lerdsirisopon, Surunchana; Tuchinda, Lawan

    2016-08-01

    To evaluate the value of physical examination as a monitoring tool during subcortical resection in awake craniotomy patients and surgical outcomes. Authors reviewed medical records of patients underwent awake craniotomy with continuous physical examination for pathology adjacent to the eloquent area. Between January 2006 and August 2015, there were 37 patients underwent awake craniotomy with continuous physical examination. Pathology was located in the left cerebral hemisphere in 28 patients (75.7%). Thirty patients (81.1%) had neuroepithelial tumors. Degree of resections were defined as total, subtotal, and partial in 16 (43.2%), 11 (29.7%) and 10 (27.0%) patients, respectively. Median follow up duration was 14 months. The reasons for termination of subcortical resection were divided into 3 groups as follows: 1) by anatomical landmark with the aid of neuronavigation in 20 patients (54%), 2) by reaching subcortical stimulation threshold in 8 patients (21.6%), and 3) by abnormal physical examination in 9 patients (24.3%). Among these 3 groups, there were statistically significant differences in the intraoperative (p=0.002) and early postoperative neurological deficit (p=0.005) with the lowest deficit in neuronavigation group. However, there were no differences in neurological outcome at later follow up (3-months p=0.103; 6-months p=0.285). There were no differences in the degree of resection among the groups. Continuous physical examination has shown to be of value as an additional layer of monitoring of subcortical white matter during resection and combining several methods may help increase the efficacy of mapping and monitoring of subcortical functions. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Subcortical grey matter changes in untreated, early stage Parkinson's disease without dementia.

    PubMed

    Lee, Hye Mi; Kwon, Kyum-Yil; Kim, Min-Jik; Jang, Ji-Wan; Suh, Sang-Il; Koh, Seong-Beom; Kim, Ji Hyun

    2014-06-01

    Previous MRI studies have investigated cortical or subcortical grey matter changes in patients with Parkinson's disease (PD), yielding inconsistent findings between the studies. We therefore sought to determine whether focal cortical or subcortical grey matter changes may be present from the early disease stage. We recruited 49 untreated, early stage PD patients without dementia and 53 control subjects. Voxel-based morphometry was used to evaluate cortical grey matter changes, and automated volumetry and shape analysis were used to assess volume changes and shape deformation of the subcortical grey matter structures, respectively. Voxel-based morphometry showed neither reductions nor increases in grey matter volume in patients compared to controls. Compared to controls, PD patients had significant reductions in adjusted volumes of putamen, nucleus accumbens, and hippocampus (corrected p < 0.05). Vertex-based shape analysis showed regionally contracted area on the posterolateral and ventromedial putamen bilaterally in PD patients (corrected p < 0.05). No correlations were found between cortical and subcortical grey matter and clinical variables representing disease duration and severity. Our results suggest that untreated, early stage PD without dementia is associated with volume reduction and shape deformation of subcortical grey matter, but not with cortical grey matter reduction. Our findings of structural changes in the posterolateral putamen and ventromedial putamen/nucleus accumbens could provide neuroanatomical basis for the involvement of motor and limbic striatum, further implicating motor and non-motor symptoms in PD, respectively. Early hippocampal involvement might be related to the risk for developing dementia in PD patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. 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

  13. DNA methyltransferase inhibitor RG108 and histone deacetylase inhibitors cooperate to enhance NB4 cell differentiation and E-cadherin re-expression by chromatin remodelling.

    PubMed

    Savickiene, Jurate; Treigyte, Grazina; Jazdauskaite, Arune; Borutinskaite, Veronika-Viktorija; Navakauskiene, Ruta

    2012-11-01

    Epigenetic silencing of cancer-related genes by abnormal methylation and the reversal of this process by DNA methylation inhibitors represents a promising strategy in cancer therapy. As DNA methylation affects gene expression and chromatin structure, we investigated the effects of novel DNMT (DNA methyltransferase) inhibitor, RG108, alone and in its combinations with structurally several HDAC (histone deacetylase) inhibitors [sodium PB (phenyl butyrate) or BML-210 (N-(2-aminophenyl)-N'phenyloctanol diamine), and all-trans RA (retinoic acid)] in the human PML (promyelocytic leukaemia) NB4 cells. RG108 at different doses from 20 to 100 μM caused time-, but not a dose-dependent inhibition of NB4 cell proliferation without cytotoxicity. Temporal pretreatment with RG108 before RA resulted in a dose-dependent cell growth inhibition and remarkable acceleration of granulocytic differentiation. Prolonged treatments with RG108 and RA in the presence of HDAC inhibitors significantly increased differentiation. RG108 caused time-dependent re-expression of methylation-silenced E-cadherin, with increase after temporal or continuous treatments with RG108 and RA, or RA together with PB in parallel, in cell maturation, suggesting the role of E-cadherin as a possible therapeutic marker. These processes required both PB-induced hyperacetylation of histone H4 and trimethylation of histone H3 at lysine 4, indicating the cooperative action of histone modifications and DNA methylation/demethylation in derepression of E-cadherin. This work provides novel experimental evidence of the beneficial role of the DNMT inhibitor RG108 in combinations with RA and HDACIs in the effective differentiation of human PML based on epigenetics.

  14. 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

  15. Subcortical and cortical structural central nervous system changes and attention processing deficits in preschool-aged children with prenatal methamphetamine and tobacco exposure.

    PubMed

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

    2012-01-01

    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. 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. 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. Our results suggest that PME and PTE may have distinct differential cortical effects on the developing central nervous system. Additionally, PME may be associated with subtle deficits in attention

  16. 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

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

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

    PubMed Central

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

    2015-01-01

    SUMMARY 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. PMID:26235048

  3. 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

  4. Musical experience and neural efficiency: effects of training on subcortical processing of vocal expressions of emotion.

    PubMed

    Strait, Dana L; Kraus, Nina; Skoe, Erika; Ashley, Richard

    2009-02-01

    Musicians exhibit enhanced perception of emotion in speech, although the biological foundations for this advantage remain unconfirmed. In order to gain a better understanding for the influences of musical experience on neural processing of emotionally salient sounds, we recorded brainstem potentials to affective human vocal sounds. Musicians showed enhanced time-domain response magnitude to the most spectrally complex portion of the stimulus and decreased magnitude to the more periodic, less complex portion. Enhanced phase-locking to stimulus periodicity was likewise seen in musicians' responses to the complex portion. These results suggest that auditory expertise engenders both enhancement and efficiency of subcortical neural responses that are intricately connected with acoustic features important for the communication of emotional states. Our findings provide the first biological evidence for behavioral observations indicating that musical training enhances the perception of vocally expressed emotion in addition to establishing a subcortical role in the auditory processing of emotional cues.

  5. Voluntary activation of ankle muscles is accompanied by subcortical facilitation of their antagonists

    PubMed Central

    Geertsen, Svend S; Zuur, Abraham T; Nielsen, Jens B

    2010-01-01

    Flexion and extension movements are organized reciprocally, so that extensor motoneurones in the spinal cord are inhibited when flexor muscles are active and vice versa. During and just prior to dorsiflexion of the ankle, soleus motoneurones are thus inhibited as evidenced by a depression of the soleus H-reflex. It is therefore surprising that soleus motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) have been found not to be reduced and even facilitated during a voluntary dorsiflexion. The objective of this study was to investigate if MEPs, evoked by TMS, show a similar facilitation prior to and at the onset of contraction of muscles that are antagonists to the muscle in which the MEP is evoked and if so, examine the origin of such a facilitatory motor programme. Eleven seated subjects reacted to an auditory cue by contracting either the tibialis anterior (TA) or soleus muscle of the left ankle. TMS was applied to the hotspot of TA and soleus muscles on separate days. Stimuli were delivered prior to and at the beginning of contraction. Soleus MEPs were significantly facilitated when TMS was applied 50 ms prior to onset of plantar flexion. Surprisingly, soleus MEPs were also facilitated (although to a lesser extent) at a similar time in relation to the onset of dorsiflexion. TA MEPs were facilitated 50 ms prior to onset of dorsiflexion and neither depressed nor facilitated prior to plantar flexion. No difference was found between the facilitation of the soleus MEP and motor evoked responses to cervicomedullary stimulation prior to dorsiflexion, suggesting that the increased soleus MEPs were not caused by changes at a cortical level. This was confirmed by the observation that short-latency facilitation of the soleus H-reflex by subthreshold TMS was increased prior to plantar flexion, but not prior to dorsiflexion. These findings suggest that voluntary contraction at the ankle is accompanied by preceding facilitation of antagonists by

  6. 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

  7. Cerebrospinal fluid biomarkers for Alzheimer disease and subcortical axonal damage in 5,542 clinical samples

    PubMed Central

    2013-01-01

    Introduction The neuronal loss in Alzheimer disease (AD) has been described to affect grey matter in the cerebral cortex. However, in the elderly, AD pathology is likely to occur together with subcortical axonal degeneration on the basis of cerebrovascular disease. Therefore, we hypothesized that biomarkers for AD and subcortical axonal degeneration would correlate in patients undergoing testing for dementia biomarkers, particularly in older age groups. Methods We performed correlation and cluster analyses of cerebrospinal fluid (CSF) biomarker data from 5,542 CSF samples analyzed in our routine clinical neurochemistry laboratory in 2010 through 2012 for the established CSF AD biomarkers total tau (T-tau), phosphorylated-tau (P-tau), amyloid β1-42 (Aβ42), and for neurofilament light (NFL), which is a protein expressed in large-caliber myelinated axons, the CSF levels of which correlate with subcortical axonal injury. Results Aβ42, T-tau, and P-tau correlated with NFL. By cluster analysis, we found a bimodal data distribution in which a group with a low Aβ42/P-tau ratio (suggesting AD pathology) had high levels of NFL. High levels of NFL also correlated with the presence of an AD biomarker pattern defined by Aβ42/P-tau and T-tau. Only 29% of those with an AD biomarker signature had normal NFL levels. Age was a possible confounding factor for the associations between NFL and established AD biomarkers, but in a logistic regression analysis, both age and NFL independently predicted the AD biomarker pattern. Conclusions The association between an AD-like signature using the established biomarkers Aβ42, T-tau, and P-tau with increased levels of NFL provides in vivo evidence of an association between AD and subcortical axonal degeneration in this uniquely large dataset of CSF samples tested for dementia biomarkers. PMID:24479774

  8. 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. © 2016 Wiley Periodicals, Inc.

  9. 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

  10. Dementia of adult polyglucosan body disease. Evidence of cortical and subcortical dysfunction.

    PubMed

    Rifai, Z; Klitzke, M; Tawil, R; Kazee, A M; Shanske, S; DiMauro, S; Griggs, R C

    1994-01-01

    To characterize the dementia associated with adult polyglucosan body disease (APBD) and to correlate the cognitive deficits with abnormalities found on magnetic resonance imaging (MRI). Quantitative neuropsychological testing and MRI in one man with APBD and a review of the literature. The dementia of APBD affects cortical and subcortical functions. The cognitive deficits correlate with MRI findings of cortical atrophy and white-matter abnormalities. Neuropsychological testing and MRI are helpful in the evaluation of patients with APBD.

  11. Posterior SMA Syndrome following subcortical stroke: contralateral akinesia reversed by visual feedback.

    PubMed

    Radman, Narges; Cacioppo, Stephanie; Spierer, Lucas; Schmidlin, Eric; Mayer, Eugène; Annoni, Jean-Marie

    2013-11-01

    The supplementary motor area (SMA) plays a key role in motor programming and production and is involved in internally-cued movements. In neurological populations, SMA syndrome following a lesion to the "SMA proper" is characterized by transient impairment of voluntary movements and motor sequences. This syndrome is assumed to follow on from an interruption of the motor cortico-subcortical loop, and some case reports indicate that such a syndrome could occur after a brain lesion isolating the SMA from subcortical structures. To characterize the pattern of motor impairments in a patient whose stroke disconnects the SMA from the subcortical motor loop. A patient developed a moderate transient left hemiparesis following a subcortical stroke in the right anterior cerebral artery area, which disconnected the SMA from basal ganglia. Eight days after the stroke, when the hemiparesis had regressed, the patient presented a specific SMA motor disorder of the left hand which manifested as an akinesia and was exacerbated when his visual attention was not directed towards his hand. We assessed finger tapping with left and right hands, eyes closed and open, in the left and right hemispace. We indexed movement speed as the number of taps filmed over 5-s periods. Left motor weakness (grasping strength of right hand: 49 kg and left hand: 41 kg) was resolved in a week. Ideomotor and ideational gestures and motor sequences were preserved. On the tapping task, left-hand tapping was slower than right-hand tapping. Critically, visual feedback improved tapping speed for the left, but not for the right, hand. The hemispace of the task execution had no effect on tapping performance. Our results suggest that SMA-basal ganglia disconnection decreases contralateral movement initiation and maintenance and this effect is partly compensated by visual cues. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. 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.

  13. [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.

  14. 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

  15. Expanded functional coupling of subcortical nuclei with the motor resting-state network in multiple sclerosis.

    PubMed

    Dogonowski, Anne-Marie; Siebner, Hartwig R; Sørensen, Per Soelberg; Wu, Xingchen; Biswal, Bharat; Paulson, Olaf B; Dyrby, Tim B; Skimminge, Arnold; Blinkenberg, Morten; Madsen, Kristoffer H

    2013-04-01

    Multiple sclerosis (MS) impairs signal transmission along cortico-cortical and cortico-subcortical connections, affecting functional integration within the motor network. Functional magnetic resonance imaging (fMRI) during motor tasks has revealed altered functional connectivity in MS, but it is unclear how much motor disability contributed to these abnormal functional interaction patterns. To avoid any influence of impaired task performance, we examined disease-related changes in functional motor connectivity in MS at rest. A total of 42 patients with MS and 30 matched controls underwent a 20-minute resting-state fMRI session at 3 Tesla. Independent component analysis was applied to the fMRI data to identify disease-related changes in motor resting-state connectivity. Patients with MS showed a spatial expansion of motor resting-state connectivity in deep subcortical nuclei but not at the cortical level. The anterior and middle parts of the putamen, adjacent globus pallidus, anterior and posterior thalamus and the subthalamic region showed stronger functional connectivity with the motor network in the MS group compared with controls. MS is characterised by more widespread motor connectivity in the basal ganglia while cortical motor resting-state connectivity is preserved. The expansion of subcortical motor resting-state connectivity in MS indicates less efficient funnelling of neural processing in the executive motor cortico-basal ganglia-thalamo-cortical loops.

  16. 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

  17. Lack of gender influence on cortical and subcortical gray matter development in childhood-onset schizophrenia.

    PubMed

    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

    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. 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. 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). Sex appears to play a similar role in cortical and subcortical GM development in COS as it does in normally developing children.

  18. 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. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. Stereotactic use of the 980-nm diode laser in rat cortical and subcortical tissues

    NASA Astrophysics Data System (ADS)

    Guelsoy, Murat; Celikel, Tansu; Kurtkaya, Ozlem; Sav, Aydin; Kurt, Adnan; Canbeyli, Resit; Cilesiz, Inci F.

    2001-01-01

    The use of 980 nm diode laser irradiation within cortical tissue was investigated by the author's previous work. In the present study the lesions created in cortical and subcortical tissues and lesioning effects of diode laser applied in continuous and pulsed regimes were compared. In vivo stereotaxic neurosurgical procedure was performed on female Wistar rats' cortical and subcortical tissues. 980 nm diode laser was applied in two different regimes, cw and pulsed wave respectively. Lesion dimensions were measured and compared. The lasing parameters were found suitable for both brain regions. No significant difference was found between tissues. Lesions diameters varied in the range of 1.0-9.0 mm. Histological examination revealed data for a limited thermal damage in the surrounding tissue for all lesions. Cortical and subcortical tissues did not show significant differences due to same amount of energy delivered. The lasing regime did not influence the dimensions of lesions. Applied energy was found the key element determining the amount of lesion. Results were consistent with the findings found in the previous dosimetry studies.

  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. Altered structural and functional connectivity between the bilateral primary motor cortex in unilateral subcortical stroke

    PubMed Central

    Zhang, Yong; Li, Kuang-Shi; Ning, Yan-Zhe; Fu, Cai-Hong; Liu, Hong-Wei; Han, Xiao; Cui, Fang-Yuan; Ren, Yi; Zou, Yi-Huai

    2016-01-01

    Abstract 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. PMID:27495109

  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. Copyright © 2015 Elsevier Inc. All rights reserved.

  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. Changes of Brain Connectivity in the Primary Motor Cortex After Subcortical Stroke: A Multimodal Magnetic Resonance Imaging Study.

    PubMed

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

    2016-02-01

    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.

  10. Distinct Subcortical Volume Alterations in Pediatric and Adult OCD: A Worldwide Meta- and Mega-Analysis.

    PubMed

    Boedhoe, Premika S W; Schmaal, Lianne; Abe, Yoshinari; Ameis, Stephanie H; Arnold, Paul D; Batistuzzo, Marcelo C; Benedetti, Francesco; Beucke, Jan C; Bollettini, Irene; Bose, Anushree; Brem, Silvia; Calvo, Anna; Cheng, Yuqi; Cho, Kang Ik K; Dallaspezia, Sara; Denys, Damiaan; Fitzgerald, Kate D; Fouche, Jean-Paul; Giménez, Mònica; Gruner, Patricia; Hanna, Gregory L; Hibar, Derrek P; Hoexter, Marcelo Q; Hu, Hao; Huyser, Chaim; Ikari, Keisuke; Jahanshad, Neda; Kathmann, Norbert; Kaufmann, Christian; Koch, Kathrin; Kwon, Jun Soo; Lazaro, Luisa; Liu, Yanni; Lochner, Christine; Marsh, Rachel; Martínez-Zalacaín, Ignacio; Mataix-Cols, David; Menchón, José M; Minuzzi, Luciano; Nakamae, Takashi; Nakao, Tomohiro; Narayanaswamy, Janardhanan C; Piras, Fabrizio; Piras, Federica; Pittenger, Christopher; Reddy, Y C Janardhan; Sato, Joao R; Simpson, H Blair; Soreni, Noam; Soriano-Mas, Carles; Spalletta, Gianfranco; Stevens, Michael C; Szeszko, Philip R; Tolin, David F; Venkatasubramanian, Ganesan; Walitza, Susanne; Wang, Zhen; van Wingen, Guido A; Xu, Jian; Xu, Xiufeng; Yun, Je-Yeon; Zhao, Qing; Thompson, Paul M; Stein, Dan J; van den Heuvel, Odile A

    2017-01-01

    Structural brain imaging studies in obsessive-compulsive disorder (OCD) have produced inconsistent findings. This may be partially due to limited statistical power from relatively small samples and clinical heterogeneity related to variation in illness profile and developmental stage. To address these limitations, the authors conducted meta- and mega-analyses of data from OCD sites worldwide. T1 images from 1,830 OCD patients and 1,759 control subjects were analyzed, using coordinated and standardized processing, to identify subcortical brain volumes that differ between OCD patients and healthy subjects. The authors performed a meta-analysis on the mean of the left and right hemisphere measures of each subcortical structure, and they performed a mega-analysis by pooling these volumetric measurements from each site. The authors additionally examined potential modulating effects of clinical characteristics on morphological differences in OCD patients. The meta-analysis indicated that adult patients had significantly smaller hippocampal volumes (Cohen's d=-0.13; % difference=-2.80) and larger pallidum volumes (d=0.16; % difference=3.16) compared with adult controls. Both effects were stronger in medicated patients compared with controls (d=-0.29, % difference=-4.18, and d=0.29, % difference=4.38, respectively). Unmedicated pediatric patients had significantly larger thalamic volumes (d=0.38, % difference=3.08) compared with pediatric controls. None of these findings were mediated by sample characteristics, such as mean age or scanning field strength. The mega-analysis yielded similar results. The results indicate different patterns of subcortical abnormalities in pediatric and adult OCD patients. The pallidum and hippocampus seem to be of importance in adult OCD, whereas the thalamus seems to be key in pediatric OCD. These findings highlight the potential importance of neurodevelopmental alterations in OCD and suggest that further research on neuroplasticity in OCD

  11. 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

  12. Regional Brain Differences in Cortical Thickness, Surface Area and Subcortical Volume in Individuals with Williams Syndrome

    PubMed Central

    Meda, Shashwath A.; Pryweller, Jennifer R.; Thornton-Wells, Tricia A.

    2012-01-01

    Williams syndrome (WS) is a rare genetic neurodevelopmental disorder characterized by increased non-social anxiety, sensitivity to sounds and hypersociability. Previous studies have reported contradictory findings with regard to regional brain variation in WS, relying on only one type of morphological measure (usually volume) in each study. The present study aims to contribute to this body of literature and perhaps elucidate some of these discrepancies by examining concurrent measures of cortical thickness, surface area and subcortical volume between WS subjects and typically-developing (TD) controls. High resolution MRI scans were obtained on 31 WS subjects and 50 typically developing control subjects. We derived quantitative regional estimates of cortical thickness, cortical surface area, and subcortical volume using FreeSurfer software. We evaluated between-group ROI differences while controlling for total intracranial volume. In post-hoc exploratory analyses within the WS group, we tested for correlations between regional brain variation and Beck Anxiety Inventory scores. Consistent with our hypothesis, we detected complex patterns of between-group cortical variation, which included lower surface area in combination with greater thickness in the following cortical regions: post central gyrus, cuneus, lateral orbitofrontal cortex and lingual gyrus. Additional cortical regions showed between-group differences in one (but not both) morphological measures. Subcortical volume was lower in the basal ganglia and the hippocampus in WS versus TD controls. Exploratory correlations revealed that anxiety scores were negatively correlated with gray matter surface area in insula, OFC, rostral middle frontal, superior temporal and lingual gyrus. Our results were consistent with previous reports showing structural alterations in regions supporting the socio-affective and visuospatial impairments in WS. However, we also were able to effectively capture novel and complex

  13. Regional brain differences in cortical thickness, surface area and subcortical volume in individuals with Williams syndrome.

    PubMed

    Meda, Shashwath A; Pryweller, Jennifer R; Thornton-Wells, Tricia A

    2012-01-01

    Williams syndrome (WS) is a rare genetic neurodevelopmental disorder characterized by increased non-social anxiety, sensitivity to sounds and hypersociability. Previous studies have reported contradictory findings with regard to regional brain variation in WS, relying on only one type of morphological measure (usually volume) in each study. The present study aims to contribute to this body of literature and perhaps elucidate some of these discrepancies by examining concurrent measures of cortical thickness, surface area and subcortical volume between WS subjects and typically-developing (TD) controls. High resolution MRI scans were obtained on 31 WS subjects and 50 typically developing control subjects. We derived quantitative regional estimates of cortical thickness, cortical surface area, and subcortical volume using FreeSurfer software. We evaluated between-group ROI differences while controlling for total intracranial volume. In post-hoc exploratory analyses within the WS group, we tested for correlations between regional brain variation and Beck Anxiety Inventory scores. Consistent with our hypothesis, we detected complex patterns of between-group cortical variation, which included lower surface area in combination with greater thickness in the following cortical regions: post central gyrus, cuneus, lateral orbitofrontal cortex and lingual gyrus. Additional cortical regions showed between-group differences in one (but not both) morphological measures. Subcortical volume was lower in the basal ganglia and the hippocampus in WS versus TD controls. Exploratory correlations revealed that anxiety scores were negatively correlated with gray matter surface area in insula, OFC, rostral middle frontal, superior temporal and lingual gyrus. Our results were consistent with previous reports showing structural alterations in regions supporting the socio-affective and visuospatial impairments in WS. However, we also were able to effectively capture novel and complex

  14. 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.

  15. White matter injury restoration after stem cell administration in subcortical ischemic stroke.

    PubMed

    Otero-Ortega, Laura; Gutiérrez-Fernández, María; Ramos-Cejudo, Jaime; Rodríguez-Frutos, Berta; Fuentes, Blanca; Sobrino, Tomás; Hernanz, Teresa Navarro; Campos, Francisco; López, Juan Antonio; Cerdán, Sebastián; Vázquez, Jesús; Díez-Tejedor, Exuperio

    2015-06-19

    Despite its high incidence, nerve fiber (axon and myelin) damage after cerebral infarct has not yet been extensively investigated. The aim of this study was to investigate white matter repair after adipose-derived mesenchymal stem cell (ADMSC) administration in an experimental model of subcortical stroke. Furthermore, we aimed to analyze the ADMSC secretome and whether this could be implicated in this repair function. An animal model of subcortical ischemic stroke with white matter affectation was induced in rats by injection of endothelin-1. At 24 hours, 2 × 10(6) ADMSC were administered intravenously to the treatment group. Functional evaluation, lesion size, fiber tract integrity, cell death, proliferation, white matter repair markers (Olig-2, NF, and MBP) and NogoA were all studied after sacrifice (7 days and 28 days). ADMSC migration and implantation in the brain as well as proteomics analysis and functions of the secretome were also analyzed. Neither ADMSC migration nor implantation to the brain was observed after ADMSC administration. In contrast, ADMSC implantation was detected in peripheral organs. The treatment group showed a smaller functional deficit, smaller lesion area, less cell death, more oligodendrocyte proliferation, more white matter connectivity and higher amounts of myelin formation. The treated animals also showed higher levels of white matter-associated markers in the injured area than the control group. Proteomics analysis of the ADMSC secretome identified 2,416 proteins, not all of them previously described to be involved in brain plasticity. White matter integrity in subcortical stroke is in part restored by ADMSC treatment; this is mediated by repair molecular factors implicated in axonal sprouting, remyelination and oligodendrogenesis. These findings are associated with improved functional recovery after stroke.

  16. Morphometric changes in subcortical structures of the central auditory pathway in mice with bilateral nodular heterotopia.

    PubMed

    Truong, Dongnhu T; Rendall, Amanda R; Rosen, Glenn D; Fitch, R Holly

    2015-04-01

    Malformations of cortical development (MCD) have been observed in human reading and language impaired populations. Injury-induced MCD in rodent models of reading disability show morphological changes in the auditory thalamic nucleus (medial geniculate nucleus; MGN) and auditory processing impairments, thus suggesting a link between MCD, MGN, and auditory processing behavior. Previous neuroanatomical examination of a BXD29 recombinant inbred strain (BXD29-Tlr4(lps-2J)/J) revealed MCD consisting of bilateral subcortical nodular heterotopia with partial callosal agenesis. Subsequent behavioral characterization showed a severe impairment in auditory processing-a deficient behavioral phenotype seen across both male and female BXD29-Tlr4(lps-2J)/J mice. In the present study we expanded upon the neuroanatomical findings in the BXD29-Tlr4(lps-2J)/J mutant mouse by investigating whether subcortical changes in cellular morphology are present in neural structures critical to central auditory processing (MGN, and the ventral and dorsal subdivisions of the cochlear nucleus; VCN and DCN, respectively). Stereological assessment of brain tissue of male and female BXD29-Tlr4(lps-2J)/J mice previously tested on an auditory processing battery revealed overall smaller neurons in the MGN of BXD29-Tlr4(lps-2J)/J mutant mice in comparison to BXD29/Ty coisogenic controls, regardless of sex. Interestingly, examination of the VCN and DCN revealed sexually dimorphic changes in neuronal size, with a distribution shift toward larger neurons in female BXD29-Tlr4(lps-2J)/J brains. These effects were not seen in males. Together, the combined data set supports and further expands the observed co-occurrence of MCD, auditory processing impairments, and changes in subcortical anatomy of the central auditory pathway. The current stereological findings also highlight sex differences in neuroanatomical presentation in the presence of a common auditory behavioral phenotype. Copyright © 2014 Elsevier B

  17. 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.

  18. Involvement of Subcortical Brain Structures During Olfactory Stimulation in Multiple Chemical Sensitivity.

    PubMed

    Alessandrini, Marco; Micarelli, Alessandro; Chiaravalloti, Agostino; Bruno, Ernesto; Danieli, Roberta; Pierantozzi, Mariangela; Genovesi, Giuseppe; Öberg, Johanna; Pagani, Marco; Schillaci, Orazio

    2016-03-01

    Multiple chemical sensitivity (MCS) patients usually react to odour compounds and the majority of neuroimaging studies assessed, especially at the cortical level, many olfactory-related correlates. The purpose of the present study was to depict sub-cortical metabolic changes during a neutral (NC) and pure (OC) olfactory stimulation by using a recently validated (18)F-2-fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography/computer tomography procedure in 26 MCS and 11 healthy (HC) resting subjects undergoing a battery of clinical tests. Twelve subcortical volumes of interest were identified by the automated anatomical labeling library and normalized to thalamus FDG uptake. In both groups, when comparing OC to NC, the within-subjects ANOVA demonstrated a relative decreased metabolism in bilateral putamen and hippocampus and a relative increased metabolism in bilateral amygdala, olfactory cortex (OLF), caudate and pallidum. The between-groups ANOVA demonstrated in MCS a significant higher metabolism in bilateral OLF during NC. As in HC subjects negative correlations were found in OC between FDG uptake in bilateral amygdala and hippocampus and odor pleasantness scale, the latter positively correlated with MCS subjects' bilateral putamen FDG uptake in OC. Besides FDG uptake resemblances in both groups were found, for the first time a relative higher metabolism increase in OLF in MCS subjects at rest with respect to HC was found. When merging this aspect to the different subcortical FDG uptake correlations patterns in the two groups, the present study demonstrated to describe a peculiar metabolic index of behavioral and neurological aspects of MCS complaints.

  19. Motor imagery after subcortical stroke: a functional magnetic resonance imaging study.

    PubMed

    Sharma, Nikhil; Simmons, Lucy H; Jones, P Simon; Day, Diana J; Carpenter, T Adrian; Pomeroy, Valerie M; Warburton, Elizabeth A; Baron, Jean-Claude

    2009-04-01

    In recovered subcortical stroke, the pattern of motor network activation during motor execution can appear normal or not, depending on the task. Whether this applies to other aspects of motor function is unknown. We used functional MRI to assess motor imagery (MI), a promising new approach to improve motor function after stroke, and contrasted it to motor execution. Twenty well-recovered patients with hemiparetic subcortical stroke (14 males; mean age, 66.5 years) and 17 aged-matched control subjects were studied. Extensive behavioral screening excluded 8 patients and 4 control subjects due to impaired MI abilities. Subjects performed MI and motor execution of a paced finger-thumb opposition sequence using a functional MRI paradigm that monitored compliance. Activation within the primary motor cortex (BA4a and 4p), dorsal premotor, and supplementary motor areas was examined. The pattern of activation during affected-hand motor execution was not different from control subjects. Affected-hand MI activation was also largely similar to control subjects, including involvement of BA4, but with important differences: (1) unlike control subjects and the nonaffected hand, activation in BA4a and dorsal premotor was not lower during MI as compared with motor execution; (2) the hemispheric balance of BA4p activation was significantly less lateralized than control subjects; and (3) ipsilesional BA4p activation positively correlated with motor performance. In well-recovered subcortical stroke, the motor system, including ipsilesional BA4, is activated during MI despite the lesion. It, however, remains disorganized in proportion to residual motor impairment. Thus, components of movement upstream from execution appear differentially affected after stroke and could be targeted by rehabilitation in more severely affected patients.

  20. 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.

  1. 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.

  2. 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. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Disulfiram and its novel derivative sensitize prostate cancer cells to the growth regulatory mechanisms of the cell by re-expressing the epigenetically repressed tumor suppressor-estrogen receptor β.

    PubMed

    Sharma, Vikas; Verma, Vikas; Lal, Nand; Yadav, Santosh K; Sarkar, Saumya; Mandalapu, Dhanaraju; Porwal, Konica; Rawat, Tara; Maikhuri, J P; Rajender, Singh; Sharma, V L; Gupta, Gopal

    2016-11-01

    Estrogen Receptor-β (ER-β), a tumor-suppressor in prostate cancer, is epigenetically repressed by hypermethylation of its promoter. DNA-methyltransferases (DNMTs), which catalyze the transfer of methyl-groups to CpG islands of gene promoters, are overactive in cancers and can be inhibited by DNMT-inhibitors to re-express the tumor suppressors. The FDA-approved nucleoside DNMT-inhibitors like 5-Azacytidine and 5-Aza-deoxycytidine carry notable concerns due to their off-target toxicity, therefore non-nucleoside DNMT inhibitors are desirable for prolonged epigenetic therapy. Disulfiram (DSF), an antabuse drug, inhibits DNMT and prevents proliferation of cells in prostate and other cancers, plausibly through the re-expression of tumor suppressors like ER-β. To increase the DNMT-inhibitory activity of DSF, its chemical scaffold was optimized and compound-339 was discovered as a doubly potent DSF-derivative with similar off-target toxicity. It potently and selectively inhibited cell proliferation of prostate cancer (PC3/DU145) cells in comparison to normal (non-cancer) cells by promoting cell-cycle arrest and apoptosis, accompanied with inhibition of total DNMT activity, and re-expression of ER-β (mRNA/protein). Bisulfite-sequencing of ER-β promoter revealed that compound-339 demethylated CpG sites more efficaciously than DSF, restoring near-normal methylation status of ER-β promoter. Compound-339 docked on to the MTase domain of DNMT1 with half the energy of DSF. In xenograft mice-model, the tumor volume regressed by 24% and 50% after treatment with DSF and compound-339, respectively, with increase in ER-β expression. Apparently both compounds inhibit prostate cancer cell proliferation by re-expressing the epigenetically repressed tumor-suppressor ER-β through inhibition of DNMT activity. Compound-339 presents a new lead for further study as an anti-prostate cancer agent. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  4. 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. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. 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.

  6. Look me in the eyes: constraining gaze in the eye-region provokes abnormally high subcortical activation in autism.

    PubMed

    Hadjikhani, Nouchine; Åsberg Johnels, Jakob; Zürcher, Nicole R; Lassalle, Amandine; Guillon, Quentin; Hippolyte, Loyse; Billstedt, Eva; Ward, Noreen; Lemonnier, Eric; Gillberg, Christopher

    2017-06-09

    Individuals with Autism Spectrum Disorder (ASD) seem to have difficulties looking others in the eyes, but the substrate for this behavior is not well understood. The subcortical pathway, which consists of superior colliculus, pulvinar nucleus of the thalamus, and amygdala, enables rapid and automatic face processing. A specific component of this pathway - i.e., the amygdala - has been shown to be abnormally activated in paradigms where individuals had to specifically attend to the eye-region; however, a direct examination of the effect of manipulating the gaze to the eye-regions on all the components of the subcortical system altogether has never been performed. The subcortical system is particularly important as it shapes the functional specialization of the face-processing cortex during development. Using functional MRI, we investigated the effect of constraining gaze in the eye-region during dynamic emotional face perception in groups of participants with ASD and typical controls. We computed differences in activation in the subcortical face processing system (superior colliculus, pulvinar nucleus of the thalamus and amygdala) for the same stimuli seen freely or with the gaze constrained in the eye-region. Our results show that when constrained to look in the eyes, individuals with ASD show abnormally high activation in the subcortical system, which may be at the basis of their eye avoidance in daily life.

  7. 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

  8. 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.

  9. Longitudinal Development of Cortical and Subcortical Gray Matter from Birth to 2 Years

    PubMed Central

    Shi, Feng; Woolson, Sandra L.; Knickmeyer, Rebecca C.; Short, Sarah J.; Zhu, Hongtu; Hamer, Robert M.; Styner, Martin; Shen, Dinggang

    2012-01-01

    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. PMID:22109543

  10. 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.

  11. 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

  12. 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

  13. [Subcortical dementia in HTLV-I tropical spastic paraparesis. Study of 43 cases].

    PubMed

    Cartier, L; Gormaz, A

    1999-04-01

    Central nervous system damage associated to HTLV-I does not limit itself to the spinal cord, but also involves subcortical structures, producing cognitive impairment and behavioral changes which eventually could conform a new form of subcortical dementia. To study cognitive changes in patients with HTLV-I associated myelopathy. Forty three patients (31 female) with Tropical Spastic Paraparesis, aged 52 years old as a mean and with a disease lasting a mean of 7.5 years, were studied. The diagnosis was based on clinical, radiological and neurophysiological changes. The virus was identified with ELISA, indirect immunofluorescence, Western Blot or proviral DNA identification. Cognitive assessment was done using the Wechler Adult Intelligence Scale (WAIS) and Benton Visual Retention Test (form D). Patients were grouped according to their motor disability in; 23 patients with independent spastic gait, 11 patients that needed support to walk and 9 patients unable to walk. WAIS test demonstrated cognitive impairment with special deficit in some subtests such as Digit Span, Digit Symbol, Picture Arrangement and Object Assembly. Benton Test also disclosed cognitive impairment. There was a positive relationship between cognitive and motor performance. At least 50% of patients with Tropical Spastic Paraparesis have certain degree of intellectual and affective impairment.

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

    PubMed Central

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

    2013-01-01

    Two-photon fluorescence microscopy (2PM)1 enables scientists in various fields including neuroscience2,3, embryology4, and oncology5 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 2PM within the mouse brain to the cortical layer, and imaging subcortical structures currently requires the removal of overlying brain tissue3 or the insertion of optical probes6,7. Here we demonstrate non-invasive, high resolution, in vivo imaging of subcortical structures within an intact mouse brain using three-photon fluorescence microscopy (3PM) at a spectral excitation window of 1,700 nm. Vascular structures as well as red fluorescent protein (RFP)-labeled neurons within the mouse hippocampus are imaged. The combination of the long excitation wavelength and the higher order nonlinear excitation overcomes the limitations of 2PM, enabling biological investigations to take place at greater depth within tissue. PMID:24353743

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

    PubMed

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

    2012-05-15

    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.

  16. 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.

  17. Subcortical anatomy of the lateral association fascicles of the brain: A review.

    PubMed

    Martino, Juan; De Lucas, Enrique Marco

    2014-05-01

    Precise knowledge of the connectivities of the different white matter bundles is of great value for neuroscience research. Our knowledge of subcortical anatomy has improved exponentially during recent decades owing to the development of magnetic resonance diffusion tensor imaging tractography (DTI). Although DTI tractography has led to important progress in understanding white matter anatomy, the precise trajectory and cortical connections of the subcortical bundles remain poorly determined. The recent literature was extensively reviewed in order to analyze the trajectories and cortical terminations of the lateral association fibers of the brain.The anatomy of the following tracts is reviewed: superior longitudinal fasciculus, middle longitudinal fasciculus, inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, uncinate fasciculus, frontal aslant tract, and vertical occipital fasciculus. The functional role of a tract can be inferred from its topography within the brain. Knowing the functional roles of the cortical areas connected by a certain bundle, it is possible to develop new insights into the putative functional properties of such connections. Copyright © 2014 Wiley Periodicals, Inc.

  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. Impaired ideomotor limb apraxia in cortical and subcortical dementia: a comparison of Alzheimer's and Huntington's disease.

    PubMed

    Holl, Anna K; Ille, Rottraut; Wilkinson, Leonora; Otti, Daniela V; Hödl, Elfriede; Herranhof, Brigitte; Reisinger, Karin M; Müller, Nicole; Painold, Annamaria; Holl, Etienne M; Letmaier, Martin; Bonelli, Raphael M

    2011-01-01

    Although ideomotor limb apraxia is often considered to occur only in dementia with cortical involvement like Alzheimer's disease (AD), it is also frequently seen in dementia with subcortical degeneration like Huntington's disease (HD). To assess the occurrence of ideomotor limb apraxia, 46 patients with HD (27 men) and 37 patients with AD (16 men), matched for cognitive performance, were assessed with an apraxia test battery containing tests of the imitation of meaningless hand and finger gestures, the performance of meaningful gestures and of pantomimic movements. There was a high frequency of ideomotor limb apraxia in both AD and HD patients. For the assessment of hands' imitation 13.5% of the AD patients and 41.3% of the HD patients were apraxic, for fingers' imitation 21.6% (AD) and 41.3% (HD) were apraxic, for gestures 27.0% (AD) and 32.6% (HD), and for the assessment of pantomimic movements 24.3% (AD) and 52.2% (HD) showed apraxia. In the AD patients, disease severity was related to the occurrence of apraxia. Ideomotor limb apraxia is a common sign in both groups of patients, occurring in a high percentage. For particular neuropsychological deficits, including ideomotor limb apraxia, a division of dementia in a subcortical and cortical subtype seems to be clinically not meaningful. Copyright © 2011 S. Karger AG, Basel.

  20. 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.

  1. 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

  2. NogoA Neutralization Promotes Axonal Restoration After White Matter Injury In Subcortical Stroke.

    PubMed

    Otero-Ortega, Laura; Gómez-de Frutos, Mari Carmen; Laso-García, Fernando; Sánchez-Gonzalo, Alba; Martínez-Arroyo, Arturo; Díez-Tejedor, Exuperio; Gutiérrez-Fernández, María

    2017-08-25

    Blocking axonal growth inhibitor NogoA has been of great interest for promoting axonal recovery from neurological diseases. The present study investigates the therapeutic effects of blocking NogoA, inducing functional recovery and promoting white matter repair in an experimental animal model of stroke. Adult male rats were subjected to white matter injury by subcortical ischemic stroke. Twenty-four hours after surgery, 250 ug of anti-NogoA or anti-IgG-1 were administered through the tail vein. The quantity of NogoA protein was determined by immunohistochemistry in the brain and peripheral organs. In addition, functional status, lesion size, fiber tract integrity, axonal sprouting and white matter repair markers were analyzed. Moreover, an in vitro study was performed in order to strengthen the results obtained in vivo. A lower quantity of NogoA protein was found in the brain and peripheral organs of the animals that received anti-NogoA treatment. The animals receiving anti-NogoA treatment showed significantly better results in terms of functional recovery, fiber tract integrity, axonal sprouting and white matter repair markers compared with the control group at 28 days. White matter integrity was in part restored by antibody-mediated inhibition of NogoA administration in those animals that were subjected to an axonal injury by subcortical stroke. This white matter restoration triggered functional recovery.

  3. Intraoperative Subcortical Electrical Mapping of the Optic Tract in Awake Surgery Using a Virtual Reality Headset.

    PubMed

    Mazerand, Edouard; Le Renard, Marc; Hue, Sophie; Lemée, Jean-Michel; Klinger, Evelyne; Menei, Philippe

    2017-01-01

    Brain mapping during awake craniotomy is a well-known technique to preserve neurological functions, especially the language. It is still challenging to map the optic radiations due to the difficulty to test the visual field intraoperatively. To assess the visual field during awake craniotomy, we developed the Functions' Explorer based on a virtual reality headset (FEX-VRH). The impaired visual field of 10 patients was tested with automated perimetry (the gold standard examination) and the FEX-VRH. The proof-of-concept test was done during the surgery performed on a patient who was blind in his right eye and presenting with a left parietotemporal glioblastoma. The FEX-VRH was used intraoperatively, simultaneously with direct subcortical electrostimulation, allowing identification and preservation of the optic radiations. The FEX-VRH detected 9 of the 10 visual field defects found by automated perimetry. The patient who underwent an awake craniotomy with intraoperative mapping of the optic tract using the FEX-VRH had no permanent postoperative visual field defect. Intraoperative visual field assessment with the FEX-VRH during direct subcortical electrostimulation is a promising approach to mapping the optical radiations and preventing a permanent visual field defect during awake surgery for epilepsy or tumor. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. 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. Copyright © 2015 Elsevier Inc. All rights reserved.

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

    PubMed

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

    2016-10-01

    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. 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. 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. 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.

  6. Progression of subcortical atrophy and iron deposition in multiple system atrophy: a comparison between clinical subtypes.

    PubMed

    Lee, Jae-Hyeok; Kim, Tae-Hyung; Mun, Chi-Woong; Kim, Tae-Hyoung; Han, Yong-Hee

    2015-08-01

    Magnetic resonance imaging (MRI) can be useful not only for the diagnosis of multiple system atrophy (MSA) itself, but also to distinguish between different clinical subtypes. This study aimed to investigate whether there are differences in the progression of subcortical atrophy and iron deposition between two variants of MSA. Two serial MRIs at baseline and follow-up were analyzed in eight patients with the parkinsonian variant MSA (MSA-P), nine patients with cerebellar variant MSA (MSA-C), and fifteen patients with Parkinson's disease (PD). The R2* values and volumes were calculated for the selected subcortical structures (caudate nucleus, putamen, globus pallidus, and thalamus) using an automated region-based analysis. In both volume and R2*, a higher rate of progression was identified in MSA-P patients. Volumetric analysis showed significantly more rapid progression of putamen and caudate nucleus in MSA-P than in MSA-C. With regard to R2* changes, a significant increase at follow-up and a higher rate of progression were identified in the putamen of MSA-P group compared to MSA-C and PD groups. This longitudinal study revealed different progression rates of MRI markers between MSA-P and MSA-C. Iron-related degeneration in the putamen may be more specific for MSA-P.

  7. 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.

  8. [Right hemiasomatognosia and sensation of amputation caused by left subcortical lesion. Role of callosal disconnection].

    PubMed

    Cambier, J; Elghozi, D; Graveleau, P; Lubetzki, C

    1984-01-01

    A 72-year-old right-handed hypertensive man presented with a right brachial monoplegia, and hypesthesia of the right half of the body to touch and pricking, sparing the face. A CT scan 2 weeks later showed a spontaneous hyperdense area corresponding to a left subcortical parietal hematoma. The patient used his spontaneous language to express body image disturbances: intense prolonged feeling of amputation related to the upper limb and foot on the right side, hemiasomatognosia without anosognosia, autotopagnosia. Also associated were a right-sided visual negligence and a more general inability to handle spatial data leading to a temporospatial disorientation. Mild language disorders were suggestive of subcortical aphasia: normal incitation and repetition; with semantic paraphasias, poor verbal fluency. Furthermore comprehension of orders or propositions concerning spatial data were poor. Finally, there were signs suggestive of callosal disconnection: paradoxical extinction of the left ear during dichotic listening, agraphia and anomia of the left hand, ideomotor apraxia of the left upper limb, difficulty in visual transfer. The lesion interrupted thalamic tracts to parietal regions and callosal fibers linking parieto-occipital association areas. This twofold lesion was analyzed for each of the neuropsychological disturbances observed. Certain aspect of cerebral function in this patient were reminiscent of "split-brain" disorders. The left hemisphere which "speaks" fails to understand the feelings of the right hemisphere: unfamiliarity of places, sensations of illness, resulting in an unadapted speech. The pathophysiology of feeling of amputation is discussed.

  9. 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.

  10. 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

  11. Re-expression of estrogen receptor alpha using a tetracycline-regulated gene expression system induced estrogen-mediated growth inhibition of the MDA-MB-231 breast cancer cell line.

    PubMed

    Barrón-González, Arturo; Castro Romero, Ivone

    2004-04-01

    Estrogen receptor (ER)-negative breast carcinomas are often difficult to treat with antiestrogens. This work was performed to determine if the re-expression of the human ER alpha could restore the hormone response of these cells. We have transfected the human wild-type ER alpha to an ER-negative breast cancer cell line (MDA-MB-231) using a tetracycline-regulated gene expression system. We obtained a new cell line, MDA-A4-5/2. Cell count and flow cytometry "S" phase cell fraction showed that 17-beta-estradiol induced an inhibition on the proliferation of these cells; on the contrary, the antiestrogens ICI 182 780, and tamoxifen blocked this effect. Finally, we demonstrated an induction of the endogenous progesterone receptor gene when ER alpha was present. These results suggest that the re-expression of ER alpha in ER-negative breast cancer cells recreate, at least partially, a hormone-responsive phenotype and may be useful as a therapeutic approach to control this pathology.

  12. Rescue of odontogenesis in Dmp1-deficient mice by targeted re-expression of DMP1 reveals roles for DMP1 in early odontogenesis and dentin apposition in vivo.

    PubMed

    Lu, Yongbo; Ye, Ling; Yu, Shibin; Zhang, Shubin; Xie, Yixia; McKee, Marc D; Li, Yan Chun; Kong, Juan; Eick, J David; Dallas, Sarah L; Feng, Jian Q

    2007-03-01

    Dentin matrix protein 1 (DMP1) is expressed in both pulp and odontoblast cells and deletion of the Dmp1 gene leads to defects in odontogenesis and mineralization. The goals of this study were to examine how DMP1 controls dentin mineralization and odontogenesis in vivo. Fluorochrome labeling of dentin in Dmp1-null mice showed a diffuse labeling pattern with a 3-fold reduction in dentin appositional rate compared to controls. Deletion of DMP1 was also associated with abnormalities in the dentinal tubule system and delayed formation of the third molar. Unlike the mineralization defect in Vitamin D receptor-null mice, the mineralization defect in Dmp1-null mice was not rescued by a high calcium and phosphate diet, suggesting a different effect of DMP1 on mineralization. Re-expression of Dmp1 in early and late odontoblasts under control of the Col1a1 promoter rescued the defects in mineralization as well as the defects in the dentinal tubules and third molar development. In contrast, re-expression of Dmp1 in mature odontoblasts, using the Dspp promoter, produced only a partial rescue of the mineralization defects. These data suggest that DMP1 is a key regulator of odontoblast differentiation, formation of the dentin tubular system and mineralization and its expression is required in both early and late odontoblasts for normal odontogenesis to proceed.

  13. Rescue of Odontogenesis in Dmp1-deficient Mice by Targeted Re-expression of DMP1 Reveals Roles for DMP1 in Early Odontogenesis and Dentin Apposition in vivo

    PubMed Central

    Lu, Yongbo; Ye, Ling; Yu, Shibin; Zhang, Shubin; Xie, Yixia; McKee, Marc D.; Li, Yanchun; Kong, Juan; Eick, David; Dallas, Sarah L.; Feng, Jian Q.

    2007-01-01

    Dentin matrix protein 1 (DMP1) is expressed in both pulp and odontoblast cells and deletion of the Dmp1 gene leads to defects in odontogenesis and mineralization. The goals of this study were to examine how DMP1 controls dentin mineralization and odontogenesis in vivo. Fluorochrome labeling of dentin in Dmp1-null mice showed a diffuse labeling pattern with a three-fold reduction in dentin appositional rate compared to controls. Deletion of DMP1 was also associated with abnormalities in the dentinal tubule system and delayed formation of the third molar. Unlike the mineralization defect in Vitamin D receptor null mice, the mineralization defect in Dmp1-null mice was not rescued by a high calcium and phosphate diet, suggesting that the effects of DMP1 on mineralization are locally mediated. Re-expression of Dmp1 in early and late odontoblasts under control of the Col1a1 promoter rescued the defects mineralization as well as the defects in the dentinal tubules and third molar development. In contrast, re-expression in mature odontoblasts, using the Dspp promoter, produced only a partial rescue of the mineralization defects. These data suggest that DMP1 is a key regulator of odontoblast differentiation, formation of the dentin tubular system and mineralization and its expression is required in both early and late odontoblasts for normal odontogenesis to proceed. PMID:17196192

  14. [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.

  15. 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.

  16. [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

  17. 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

  18. Achieved blood pressures in the secondary prevention of small subcortical strokes (SPS3) study: challenges and lessons learned.

    PubMed

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

    2014-08-01

    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. 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. 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%). 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. © American Journal of Hypertension, Ltd 2014. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  19. 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

  20. 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

  1. 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.

  2. 4D hyperspherical harmonic (HyperSPHARM) representation of multiple disconnected brain subcortical structures.

    PubMed

    Hosseinbor, Ameer Pasha; Chung, Moo K; Schaefer, Stacey M; van Reekum, Carien M; Peschke-Schmitz, Lara; Sutterer, Matt; Alexander, Andrew L; Davidson, Richard J

    2013-01-01

    We present a novel surface parameterization technique using hyperspherical harmonics (HSH) in representing compact, multiple, disconnected brain subcortical structures as a single analytic function. The proposed hyperspherical harmonic representation (HyperSPHARM) has many advantages over the widely used spherical harmonic (SPHARM) parameterization technique. SPHARM requires flattening 3D surfaces to 3D sphere which can be time consuming for large surface meshes, and can't represent multiple disconnected objects with single parameterization. On the other hand, HyperSPHARM treats 3D object, via simple stereographic projection, as a surface of 4D hypersphere with extremely large radius, hence avoiding the computationally demanding flattening process. HyperSPHARM is shown to achieve a better reconstruction with only 5 basis compared to SPHARM that requires more than 441.

  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. 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.

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

    PubMed Central

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

    2011-01-01

    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. PMID:22689832

  6. The role of the thalamus in the human subcortical vestibular system.

    PubMed

    Conrad, Julian; Baier, Bernhard; Dieterich, Marianne

    2014-01-01

    Most of our knowledge concerning central vestibular pathways is derived from animal studies while evidence of the functional importance and localization of these pathways in humans is less well defined. The termination of these pathways at the thalamic level in humans is even less known. In this review we summarize the findings concerning the central subcortical vestibular pathways in humans and the role of these structures in the central vestibular system with regard to anatomical localization and function. Also, we review the role of the thalamus in the pathogenesis of higher order sensory deficits such as spatial neglect, pusher syndrome or thalamic astasia and the correlation of these phenomena with findings of a vestibular tone imbalance at the thalamic level. By highlighting thalamic structures involved in vestibular signal processing and relating the different nomenclatures we hope to provide a base for future studies on thalamic sensory signal processing.

  7. 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

  8. 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.

  9. 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

  10. 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

  11. 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

  12. 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. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  13. 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

  14. Cortical and subcortical mapping of language areas: correlation of functional MRI and tractography in a 3T scanner with intraoperative cortical and subcortical stimulation in patients with brain tumors located in eloquent areas.

    PubMed

    Jiménez de la Peña, M; Gil Robles, S; Recio Rodríguez, M; Ruiz Ocaña, C; Martínez de Vega, V

    2013-01-01

    To describe the detection of cortical areas and subcortical pathways involved in language observed in MRI activation studies and tractography in a 3T MRI scanner and to correlate the findings of these functional studies with direct intraoperative cortical and subcortical stimulation. We present a series of 14 patients with focal brain tumors adjacent to eloquent brain areas. All patients underwent neuropsychological evaluation before and after surgery. All patients underwent MRI examination including structural sequences, perfusion imaging, spectroscopy, functional imaging to determine activation of motor and language areas, and 3D tractography. All patients underwent cortical mapping through cortical and subcortical stimulation during the operation to resect the tumor. Postoperative follow-up studies were done 24 hours after surgery. The correlation of motor function and of the corticospinal tract determined by functional MRI and tractography with intraoperative mapping of cortical and subcortical motor areas was complete. The eloquent brain areas of language expression and reception were strongly correlated with intraoperative cortical mapping in all but two cases (a high grade infiltrating glioma and a low grade glioma located in the frontal lobe). 3D tractography identified the arcuate fasciculus, the lateral part of the superior longitudinal fasciculus, the subcallosal fasciculus, the inferior fronto-occipital fasciculus, and the optic radiations, which made it possible to mark the limits of the resection. The correlation with the subcortical mapping of the anatomic arrangement of the fasciculi with respect to the lesions was complete. The best treatment for brain tumors is maximum resection without associated deficits, so high quality functional studies are necessary for preoperative planning. Copyright © 2011 SERAM. Published by Elsevier Espana. All rights reserved.

  15. Super-resolution imaging of subcortical white matter using stochastic optical reconstruction microscopy (STORM) and super-resolution optical fluctuation imaging (SOFI).

    PubMed

    Hainsworth, A H; Lee, S; Foot, P; Patel, A; Poon, W W; Knight, A E

    2017-07-11

    The spatial resolution of light microscopy is limited by the wavelength of visible light (the 'diffraction limit', approximately 250 nm). Resolution of sub-cellular structures, smaller than this limit, is possible with super resolution methods such as stochastic optical reconstruction microscopy (STORM) and super-resolution optical fluctuation imaging (SOFI). We aimed to resolve subcellular structures (axons, myelin sheaths and astrocytic processes) within intact white matter, using STORM and SOFI. Standard cryostat-cut sections of subcortical white matter from donated human brain tissue and from adult rat and mouse brain were labelled, using standard immunohistochemical markers (neurofilament-H, myelin-associated glycoprotein, glial fibrillary acidic protein, GFAP). Image sequences were processed for STORM (effective pixel size 8-32 nm) and for SOFI (effective pixel size 80 nm). In human, rat and mouse, subcortical white matter high-quality images for axonal neurofilaments, myelin sheaths and filamentous astrocytic processes were obtained. In quantitative measurements, STORM consistently underestimated width of axons and astrocyte processes (compared with electron microscopy measurements). SOFI provided more accurate width measurements, though with somewhat lower spatial resolution than STORM. Super resolution imaging of intact cryo-cut human brain tissue is feasible. For quantitation, STORM can under-estimate diameters of thin fluorescent objects. SOFI is more robust. The greatest limitation for super-resolution imaging in brain sections is imposed by sample preparation. We anticipate that improved strategies to reduce autofluorescence and to enhance fluorophore performance will enable rapid expansion of this approach. © 2017 British Neuropathological Society.

  16. 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

  17. 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

  18. Efficacy of two insecticides for protecting loblolly pines (Pinus taeda L.) from subcortical beetles (Coleoptera: Curculionidae and Cerambycidae)

    Treesearch

    Jordon L. Burke; James L. Hanula; Scott Horn; Jackson P. Audley; Kamal JK. Gandhi

    2012-01-01

    Tests were conducted on two insecticides (carbaryl and bifenthrin) for excluding subcortical beetles (Coleoptera: Curculionidae and Cerambycidae) from loblolly pine trees (Pinus taeda L.). Two trap designs (single- and double-pane windows) and two trapping heights (1.5 and 4m) were also evaluated for maximizing beetle catches.

  19. Genetic Patterns of Correlation Among Subcortical Volumes in Humans: Results From a Magnetic Resonance Imaging Twin Study

    PubMed Central

    Eyler, Lisa T.; Prom-Wormley, Elizabeth; Fennema-Notestine, Christine; Panizzon, Matthew S.; Neale, Michael C.; Jernigan, Terry L.; Fischl, Bruce; Franz, Carol E.; Lyons, Michael J.; Stevens, Allison; Pacheco, Jennifer; Perry, Michele E.; Schmitt, J. Eric; Spitzer, Nicholas C.; Seidman, Larry J.; Thermenos, Heidi W.; Tsuang, Ming T.; Dale, Anders M.; Kremen, William S.

    2012-01-01

    Little is known about genetic influences on the volume of subcortical brain structures in adult humans, particularly whether there is regional specificity of genetic effects. Understanding patterns of genetic covariation among volumes of subcortical structures may provide insight into the development of individual differences that have consequences for cognitive and emotional behavior and neuropsychiatric disease liability. We measured the volume of 19 subcortical structures (including brain and ventricular regions) in 404 twins (110 monozygotic and 92 dizygotic pairs) from the Vietnam Era Twin Study of Aging and calculated the degree of genetic correlation among these volumes. We then examined the patterns of genetic correlation through hierarchical cluster analysis and by principal components analysis. We found that a model with four genetic factors best fit the data: a Basal Ganglia/Thalamus factor; a Ventricular factor; a Limbic factor; and a Nucleus Accumbens factor. Homologous regions from each hemisphere loaded on the same factors. The observed patterns of genetic correlation suggest the influence of multiple genetic influences. There is a genetic organization among structures which distinguishes between brain and cerebrospinal fluid spaces and between different subcortical regions. Further study is needed to understand this genetic patterning and whether it reflects influences on early development, functionally dependent patterns of growth or pruning, or regionally specific losses due to genes involved in aging, stress response, or disease. PMID:20572207

  20. 3D fully convolutional networks for subcortical segmentation in MRI: A large-scale study.

    PubMed

    Dolz, Jose; Desrosiers, Christian; Ben Ayed, Ismail

    2017-04-24

    This study investigates a 3D and fully convolutional neural network (CNN) for subcortical brain structure segmentation in MRI. 3D CNN architectures have been generally avoided due to their computational and memory requirements during inference. We address the problem via small kernels, allowing deeper architectures. We further model both local and global context by embedding intermediate-layer outputs in the final prediction, which encourages consistency between features extracted at different scales and embeds fine-grained information directly in the segmentation process. Our model is efficiently trained end-to-end on a graphics processing unit (GPU), in a single stage, exploiting the dense inference capabilities of fully CNNs. We performed comprehensive experiments over two publicly available datasets. First, we demonstrate a state-of-the-art performance on the ISBR dataset. Then, we report a large-scale multi-site evaluation over 1112 unregistered subject datasets acquired from 17 different sites (ABIDE dataset), with ages ranging from 7 to 64 years, showing that our method is robust to various acquisition protocols, demographics and clinical factors. Our method yielded segmentations that are highly consistent with a standard atlas-based approach, while running in a fraction of the time needed by atlas-based methods and avoiding registration/normalization steps. This makes it convenient for massive multi-site neuroanatomical imaging studies. To the best of our knowledge, our work is the first to study subcortical structure segmentation on such large-scale and heterogeneous data. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Subcortical processing of speech regularities underlies reading and music aptitude in children

    PubMed Central

    2011-01-01

    Background Neural sensitivity to acoustic regularities supports fundamental human behaviors such as hearing in noise and reading. Although the failure to encode acoustic regularities in ongoing speech has been associated with language and literacy deficits, how auditory expertise, such as the expertise that is associated with musical skill, relates to the brainstem processing of speech regularities is unknown. An association between musical skill and neural sensitivity to acoustic regularities would not be surprising given the importance of repetition and regularity in music. Here, we aimed to define relationships between the subcortical processing of speech regularities, music aptitude, and reading abilities in children with and without reading impairment. We hypothesized that, in combination with auditory cognitive abilities, neural sensitivity to regularities in ongoing speech provides a common biological mechanism underlying the development of music and reading abilities. Methods We assessed auditory working memory and attention, music aptitude, reading ability, and neural sensitivity to acoustic regularities in 42 school-aged children with a wide range of reading ability. Neural sensitivity to acoustic regularities was assessed by recording brainstem responses to the same speech sound presented in predictable and variable speech streams. Results Through correlation analyses and structural equation modeling, we reveal that music aptitude and literacy both relate to the extent of subcortical adaptation to regularities in ongoing speech as well as with auditory working memory and attention. Relationships between music and speech processing are specifically driven by performance on a musical rhythm task, underscoring the importance of rhythmic regularity for both language and music. Conclusions These data indicate common brain mechanisms underlying reading and music abilities that relate to how the nervous system responds to regularities in auditory input

  2. Subcortical processing of speech regularities underlies reading and music aptitude in children.

    PubMed

    Strait, Dana L; Hornickel, Jane; Kraus, Nina

    2011-10-17

    Neural sensitivity to acoustic regularities supports fundamental human behaviors such as hearing in noise and reading. Although the failure to encode acoustic regularities in ongoing speech has been associated with language and literacy deficits, how auditory expertise, such as the expertise that is associated with musical skill, relates to the brainstem processing of speech regularities is unknown. An association between musical skill and neural sensitivity to acoustic regularities would not be surprising given the importance of repetition and regularity in music. Here, we aimed to define relationships between the subcortical processing of speech regularities, music aptitude, and reading abilities in children with and without reading impairment. We hypothesized that, in combination with auditory cognitive abilities, neural sensitivity to regularities in ongoing speech provides a common biological mechanism underlying the development of music and reading abilities. We assessed auditory working memory and attention, music aptitude, reading ability, and neural sensitivity to acoustic regularities in 42 school-aged children with a wide range of reading ability. Neural sensitivity to acoustic regularities was assessed by recording brainstem responses to the same speech sound presented in predictable and variable speech streams. Through correlation analyses and structural equation modeling, we reveal that music aptitude and literacy both relate to the extent of subcortical adaptation to regularities in ongoing speech as well as with auditory working memory and attention. Relationships between music and speech processing are specifically driven by performance on a musical rhythm task, underscoring the importance of rhythmic regularity for both language and music. These data indicate common brain mechanisms underlying reading and music abilities that relate to how the nervous system responds to regularities in auditory input. Definition of common biological underpinnings

  3. 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.

  4. 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.

  5. 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.

  6. Neuropsychiatric characteristics of PiB-negative subcortical vascular dementia versus behavioral variant frontotemporal dementia.

    PubMed

    Jung, Na-Yeon; Kim, Hee Jin; Kim, Yeo Jin; Kim, Seonwoo; Seo, Sang Won; Kim, Eun-Joo; Na, Duk L

    2016-01-01

    Neuropsychiatric symptoms of subcortical vascular dementia (SVaD) are mainly associated with damage to frontal-subcortical circuits and may be similar to symptoms of behavioral variant frontotemporal dementia (bvFTD). The aim of this study was to determine whether the neuropsychiatric manifestations of the Pittsburgh compound B (PiB)-negative SVaD and bvFTD groups differ. We compared the Caregiver-Administered Neuropsychiatry Inventory (CGA-NPI) between 48 patients with PiB(-) SVaD and 31 patients with bvFTD. A stepwise logistic regression was applied to determine the best model to predict SVaD. The SVaD group showed a higher frequency of depression, whereas the bvFTD group had a higher frequency of elation, aberrant motor behavior and appetite/eating disorders. Regarding NPI subscores, the bvFTD group had greater severity of elation, apathy, disinhibition, aberrant motor behavior and appetite/eating disorders, whereas SVaD did not have significantly higher subscores in any domains. The most predictive models that tend to find suggestions of SVaD, as opposed to bvFTD, are as follows: (1) the presence of depression and the absence of appetite/eating disorders, (2) higher NPI subscores of depression and lower NPI subscores of irritability and aberrant motor behavior. Apart from apathy, SVaD differed from bvFTD in that negative symptoms were more common in SVaD than bvFTD, whereas positive symptoms were predominant in bvFTD compared to SVaD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  7. 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

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. 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

  17. 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.

  18. 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

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

    PubMed

    Hipwell, Alison E; Guo, Chaohui; Phillips, Mary L; Swain, James E; Moses-Kolko, Eydie L

    2015-09-16

    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. 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 purported to be a prerequisite of

  20. 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

  1. Cortical and Subcortical Coordination of Visual Spatial Attention Revealed by Simultaneous EEG-fMRI Recording.

    PubMed

    Green, Jessica J; Boehler, Carsten N; Roberts, Kenneth C; Chen, Ling-Chia; Krebs, Ruth M; Song, Allen W; Woldorff, Marty G

    2017-08-16

    Visual spatial attention has been studied in humans with both electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) individually. However, due to the intrinsic limitations of each of these methods used alone, our understanding of the systems-level mechanisms underlying attentional control remains limited. Here, we examined trial-to-trial covariations of concurrently recorded EEG and fMRI in a cued visual spatial attention task in humans, which allowed delineation of both the generators and modulators of the cue-triggered event-related oscillatory brain activity underlying attentional control function. The fMRI activity in visual cortical regions contralateral to the cued direction of attention covaried positively with occipital gamma-band EEG, consistent with activation of cortical regions representing attended locations in space. In contrast, fMRI activity in ipsilateral visual cortical regions covaried inversely with occipital alpha-band oscillations, consistent with attention-related suppression of the irrelevant hemispace. Moreover, the pulvinar nucleus of the thalamus covaried with both of these spatially specific, attention-related, oscillatory EEG modulations. Because the pulvinar's neuroanatomical geometry makes it unlikely to be a direct generator of the scalp-recorded EEG, these covariational patterns appear to reflect the pulvinar's role as a regulatory control structure, sending spatially specific signals to modulate visual cortex excitability proactively. Together, these combined EEG/fMRI results illuminate the dynamically interacting cortical and subcortical processes underlying spatial attention, providing important insight not realizable using either method alone.SIGNIFICANCE STATEMENT Noninvasive recordings of changes in the brain's blood flow using functional magnetic resonance imaging and electrical activity using electroencephalography in humans have individually shown that shifting attention to a location in space

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

    PubMed

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

    2015-08-01

    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. 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. 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. 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. 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 such connections was associated with the severity of autistic traits in the ASD

  3. 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

  4. 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

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

    PubMed

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

    2015-04-01

    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.

  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. 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

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

    PubMed

    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

    2017-02-28

    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.

  10. Loss of Microstructural Integrity in the Limbic-Subcortical Networks for Acute Symptomatic Traumatic Brain Injury

    PubMed Central

    Zhu, Yanan; Li, Zhengjun; Bai, Lijun; Tao, Yin; Sun, Chuanzhu; Li, Min; Zheng, Longmei; Zhu, Bao; Yao, Jun; Zhou, Heping; Zhang, Ming

    2014-01-01

    Previous studies reported discrepant white matter diffusivity in mild traumatic brain injury (mTBI) on the base of Glasgow Coma Scale, which are unreliable for some TBI severity indicators and the frequency of missing documentation in the medical record. In the present study, we adopted the Mayo classification system for TBI severity. In this system, the mTBI is also divided into two groups as “probable and symptomatic” TBI. We aimed to investigate altered microstructural integrity in symptomatic acute TBI (<1 week) by using tract-based spatial statics (TBSS) approach. A total of 12 patients and 13 healthy volunteers were involved and underwent MRI scans including conventional scan, and SWI and DTI. All the patients had no visible lesions by using conventional and SWI neuroimaging techniques, while showing widespread declines in the fractional anisotropy (FA) of gray matter and white matter throughout the TBSS skeleton, particularly in the limbic-subcortical structures. By contrast, symptomatic TBI patients showed no significant enhanced changes in FA compared to the healthy controls. A better understanding of the acute changes occurring following symptomatic TBI may increase our understanding of neuroplasticity and continuing degenerative change, which, in turn, may facilitate advances in management and intervention. PMID:24695757

  11. 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.

  12. 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

  13. 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.

  14. 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

  15. Subcortical volumetric correlates of anxiety in familial pediatric bipolar disorder: a preliminary investigation.

    PubMed

    Simeonova, Diana I; Jackson, Valerie; Attalla, Ashraf; Karchemskiy, Asya; Howe, Meghan; Adleman, Nancy; Chang, Kiki

    2009-08-30

    Anxiety is a common comorbid condition in pediatric bipolar disorder (BD). However, there is little known about the effects of comorbidity on brain morphometry in this population. The aim of the present study was to examine subcortical correlates of anxiety in familial pediatric BD. The subject group comprised 120 children (mean age=12+/-3.3 years) with at least one parent diagnosed with BD. Bipolar offspring with BD were compared with bipolar offspring without BD on a measure of overall lifetime anxiety. A sub-sample of 20 bipolar offspring with BD (mean age=14.6+/-2.8 years) underwent magnetic resonance imaging (MRI) with a 3-T scanner. Correlational analyses were conducted between hippocampal and amygdalar volumes, and anxiety scores. The results showed significantly higher anxiety in bipolar offspring with BD compared to bipolar offspring without BD. There was a significant negative association between total hippocampal volume and anxiety scores. No significant association was found between total amygdalar volume and anxiety scores. Clinically, these findings suggest that anxiety comorbidity needs to be properly assessed and treated in the management of pediatric BD. This is the first study to show a negative association between hippocampal volume and anxiety in this population. The overlap between anxiety and familial pediatric BD suggests that anxiety may be one important area of future research in parsing out the heterogeneous nature and complex etiology of early-onset BD.

  16. 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

  17. 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.

  18. Brain-wide Maps Reveal Stereotyped Cell-Type-Based Cortical Architecture and Subcortical Sexual Dimorphism.

    PubMed

    Kim, Yongsoo; Yang, Guangyu Robert; Pradhan, Kith; Venkataraju, Kannan Umadevi; Bota, Mihail; García Del Molino, Luis Carlos; Fitzgerald, Greg; Ram, Keerthi; He, Miao; Levine, Jesse Maurica; Mitra, Partha; Huang, Z Josh; Wang, Xiao-Jing; Osten, Pavel

    2017-10-05

    The stereotyped features of neuronal circuits are those most likely to explain the remarkable capacity of the brain to process information and govern behaviors, yet it has not been possible to comprehensively quantify neuronal distributions across animals or genders due to the size and complexity of the mammalian brain. Here we apply our quantitative brain-wide (qBrain) mapping platform to document the stereotyped distributions of mainly inhibitory cell types. We discover an unexpected cortical organizing principle: sensory-motor areas are dominated by output-modulating parvalbumin-positive interneurons, whereas association, including frontal, areas are dominated by input-modulating somatostatin-positive interneurons. Furthermore, we identify local cell type distributions with more cells in the female brain in 10 out of 11 sexually dimorphic subcortical areas, in contrast to the overall larger brains in males. The qBrain resource can be further mined to link stereotyped aspects of neuronal distributions to known and unknown functions of diverse brain regions. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. Pubertal Status Associations with Reward and Threat Sensitivities and Subcortical Brain Volumes during Adolescence

    PubMed Central

    Urošević, Snežana; Collins, Paul; Muetzel, Ryan; Lim, Kelvin O.; Luciana, Monica

    2014-01-01

    Adolescence is characterized by complex developmental processes that impact behavior, biology, and social functioning. Two such adolescence-specific processes are puberty and increases in reward sensitivity. Relations between these processes are poorly understood. The present study focused on examining unique effects of puberty, age, and sex on reward and threat sensitivities and volumes of subcortical brain structures relevant for reward/threat processing in a healthy sample of 9 to 18 year-olds. Unlike age, pubertal status had a significant unique positive relationship with reward sensitivity. In addition, there was a trend for adolescent females to exhibit higher threat sensitivity with more advanced pubertal development and higher reward and threat sensitivity with older age. Similarly, there were significant puberty by sex interaction effects on striatal volumes, i.e., left nucleus accumbens and right pallidum. The present pattern of results suggests that pubertal development, independent of chronological age, is uniquely associated with reward hypersensitivity and with structural differences in striatal regions implicated in reward processing. PMID:24512818

  5. Atlas Generation for Subcortical and Ventricular Structures with its Applications in Shape Analysis

    PubMed Central

    Qiu, Anqi; Brown, Timothy; Fischl, Bruce; Ma, Jun; Miller, Michael I.

    2010-01-01

    Atlas-driven morphometric analysis has received great attention for studying anatomical shape variation across clinical populations in neuroimaging research as it provides a local coordinate representation for understanding the family of anatomic observations. We present a procedure for generating atlas of subcortical and ventricular structures, including amygdala, hippocampus, caudate, putamen, globus pallidus, thalamus, and lateral ventricles, using the large deformation diffeomorphic metric atlas generation algorithm. The atlas was built based on manually labeled volumes of 41 subjects randomly selected from the database of Open Access Series of Imaging Studies (OASIS, 10 young adults, 10 middle age adults, 10 healthy elders, and 11 patients with dementia). We show that the estimated atlas is representative of the population in terms of its metric distance to each individual subject in the population. In the application of detecting shape variations, using the estimated atlas may potentially increase statistical power in identifying group shape difference when comparing with using a single subject atlas. In shape-based classification, the metric distances between subjects and each of within-class estimated atlases construct a shape feature space, which allows for performing a variety of classification algorithms to distinguish anatomies. PMID:20129863

  6. 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

  7. Pubertal status associations with reward and threat sensitivities and subcortical brain volumes during adolescence.

    PubMed

    Urošević, Snežana; Collins, Paul; Muetzel, Ryan; Lim, Kelvin O; Luciana, Monica

    2014-08-01

    Adolescence is characterized by complex developmental processes that impact behavior, biology, and social functioning. Two such adolescence-specific processes are puberty and increases in reward sensitivity. Relations between these processes are poorly understood. The present study focused on examining unique effects of puberty, age, and sex on reward and threat sensitivities and volumes of subcortical brain structures relevant for reward/threat processing in a healthy sample of 9-18year-olds. Unlike age, pubertal status had a significant unique positive relationship with reward sensitivity. In addition, there was a trend for adolescent females to exhibit higher threat sensitivity with more advanced pubertal development and higher reward and threat sensitivity with older age. Similarly, there were significant puberty by sex interaction effects on striatal volumes, i.e., left nucleus accumbens and right pallidum. The present pattern of results suggests that pubertal development, independent of chronological age, is uniquely associated with reward hypersensitivity and with structural differences in striatal regions implicated in reward processing. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. 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.

  9. 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.

  10. 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.

  11. Local label learning (LLL) for subcortical structure segmentation: application to hippocampus segmentation.

    PubMed

    Hao, Yongfu; Wang, Tianyao; Zhang, Xinqing; Duan, Yunyun; Yu, Chunshui; Jiang, Tianzi; Fan, Yong

    2014-06-01

    Automatic and reliable segmentation of subcortical structures is an important but difficult task in quantitative brain image analysis. Multi-atlas based segmentation methods have attracted great interest due to their promising performance. Under the multi-atlas based segmentation framework, using deformation fields generated for registering atlas images onto a target image to be segmented, labels of the atlases are first propagated to the target image space and then fused to get the target image segmentation based on a label fusion strategy. While many label fusion strategies have been developed, most of these methods adopt predefined weighting models that are not necessarily optimal. In this study, we propose a novel local label learning strategy to estimate the target image's segmentation label using statistical machine learning techniques. In particular, we use a L1-regularized support vector machine (SVM) with a k nearest neighbor (kNN) based training sample selection strategy to learn a classifier for each of the target image voxel from its neighboring voxels in the atlases based on both image intensity and texture features. Our method has produced segmentation results consistently better than state-of-the-art label fusion methods in validation experiments on hippocampal segmentation of over 100 MR images obtained from publicly available and in-house datasets. Volumetric analysis has also demonstrated the capability of our method in detecting hippocampal volume changes due to Alzheimer's disease. Copyright © 2013 Wiley Periodicals, Inc.

  12. Giant subcortical high-frequency SEPs in idiopathic generalized epilepsy: a protective mechanism against seizures?

    PubMed

    Restuccia, Domenico; Valeriani, Massimiliano; Della Marca, Giacomo

    2007-01-01

    Recently, we found that high-frequency somatosensory evoked potentials (HF-SEPs), which are modulated by arousal-related structures, were abnormally enhanced during N-REM sleep in two seizure-free IGE patients [Restuccia D, Rubino M, Valeriani M, Della Marca G. Increase of brainstem high-frequency SEP subcomponents during light sleep in seizure-free epileptic patients. Clin Neurophysiol 2005; 116: 1774-1778]. Here, we aimed at verifying whether similar HF-SEP abnormalities were significantly correlated to the clinical outcome in a larger population of untreated IGE patients. Patients were classified as Juvenile Myoclonic epilepsy (JME; six patients) and Childhood or Juvenile Absence epilepsy (CAE and JAE, six patients). They were untreated because newly diagnosed, or because seizure-free. HF-SEPs from patients were compared with those obtained from 21 healthy volunteers. HF-SEPs were abnormally enhanced in all seizure-free CAE-JAE patients, whereas they were normal in all JME patients and in CAE-JAE patients with frequent seizures. Not only scalp distribution, but also dipolar source analysis suggested a subcortical origin for these enhanced subcomponents, possibly in the brainstem. The enhancement of HF-SEPs might reflect the hyperactivity of arousal-related brainstem structures; such an enhancement was found in all seizure-free CAE-JAE patients, while it was never observed in JME patients. We speculate that the hyperactivity of arousal-related brainstem structures might account for the different clinical outcome among IGE subsyndromes.

  13. 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.

  14. 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.

  15. Self-Trained Supervised Segmentation of Subcortical Brain Structures Using Multispectral Magnetic Resonance Images

    PubMed Central

    Larobina, Michele; Murino, Loredana; Cervo, Amedeo; Alfano, Bruno

    2015-01-01

    The aim of this paper is investigate the feasibility of automatically training supervised methods, such as k-nearest neighbor (kNN) and principal component discriminant analysis (PCDA), and to segment the four subcortical brain structures: caudate, thalamus, pallidum, and putamen. The adoption of supervised classification methods so far has been limited by the need to define a representative training dataset, operation that usually requires the intervention of an operator. In this work the selection of the training data was performed on the subject to be segmented in a fully automated manner by registering probabilistic atlases. Evaluation of automatically trained kNN and PCDA classifiers that combine voxel intensities and spatial coordinates was performed on 20 real datasets selected from two publicly available sources of multispectral magnetic resonance studies. The results demonstrate that atlas-guided training is an effective way to automatically define a representative and reliable training dataset, thus giving supervised methods the chance to successfully segment magnetic resonance brain images without the need for user interaction. PMID:26583131

  16. [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.

  17. 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.

  18. 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

  19. 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

  20. The subcortical hidden side of focal motor seizures: evidence from micro-recordings and local field potentials.

    PubMed

    Devergnas, Annaelle; Piallat, Brigitte; Prabhu, Shivadatta; Torres, Napoleon; Louis Benabid, Alim; David, Olivier; Chabardès, Stephan

    2012-07-01

    Focal motor seizures are characterized by transient motor behaviour that occurs simultaneously with paroxystic activity in the controlateral motor cortex. The implication of the basal ganglia has already been shown for generalized seizure but the propagation pathways from the motor cortex towards the basal ganglia during focal motor seizures are largely unknown. With a better knowledge of those pathways, a therapeutic modulation for reducing drug resistant motor epilepsy could be considered. Here, we recorded single-unit activities and local field potentials in the basal ganglia of two Macaca fascicularis in which acute focal motor seizures were induced by the injection of penicillin over the arm motor cortex territory. Each neuron was characterized using its mean firing rate and its type of firing pattern during interictal periods and seizures. Time-frequency analyses of local field potentials and electroencephalographic signals were used to assess dynamic changes occurring during seizure at a larger spatial level. The firing rate of neurons of input stages of basal ganglia (subthalamic nucleus and putamen) and those from the external part of the globus pallidus were significantly higher during seizures as compared to interictal periods. During seizures, the proportion of oscillatory neurons in subthalamic nucleus (71%), external globus pallidus (45%) and putamen (53%) significantly increased in comparison to interictal periods. Rhythmic activity was synchronized with ictal cortical spikes in external globus pallidus and subthalamic nucleus, but not in the putamen which oscillated faster than motor cortex. In contrast, no significant modification of the firing rate of the output stages of basal ganglia (internal part of the globus pallidus, substantia nigra pars reticulata) could be found during seizures. The local field potentials of subthalamic nucleus and external globus pallidus changed abruptly at the onset of the seizure, showing synchronization with the

  1. 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.

  2. Occipital lobe seizures and subcortical T2 and T2* hypointensity associated with nonketotic hyperglycemia: a case report.

    PubMed

    Sasaki, Fuyuko; Kawajiri, Sumihiro; Nakajima, Sho; Yamaguchi, Ai; Tomizawa, Yuji; Noda, Kazuyuki; Hattori, Nobutaka; Okuma, Yasuyuki

    2016-08-12

    Nonketotic hyperglycemia often causes seizures. Recently, seizures associated with nonketotic hyperglycemia have been found to be associated with subcortical T2 hypointensity on magnetic resonance imaging, especially in the occipital lobes. However, the mechanism remains unclear, although iron accumulation is suggested. We present a case of occipital lobe seizures associated with nonketotic hyperglycemia supporting the hypothesis that the mechanism of subcortical T2 hypointensity is iron accumulation using gradient-echo T2*-weighted magnetic resonance imaging. A 65-year-old Japanese man complained of intermittent pastel-colored flashing lights. On neurological examination, he also had lower right-side quadrant hemianopia. No other abnormal neurological findings were found. On laboratory analysis, his blood glucose level was 370 mg/dL, HbA1c was 11.4 %, and serum osmolarity was 326 mOsm/L. No ketones were detected in urine. A magnetic resonance imaging scan of his head showed subcortical T2 and T2* hypointensity in his left occipital lobe. Single-photon emission computed tomography with I123-N-isopropyl-iodoamphetamine revealed hyperperfusion in the left dominant occipital lobe. These magnetic resonance imaging abnormalities resolved during clinical recovery and treatment to control his blood sugar level. Therefore, a diagnosis of occipital lobe seizures associated with nonketotic hyperglycemia was made. To the best of our knowledge, this is the first case of occipital lobe seizures associated with nonketotic hyperglycemia supporting the role of iron accumulation as a mechanism for subcortical T2 hypointensity using T2*-magnetic resonance imaging.

  3. 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.

  4. 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

  5. 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

  6. Aberrant cortico-subcortical functional connectivity among women with poor motor control: toward uncovering the substrate of hyperkinetic perseveration.

    PubMed

    Suchy, Yana; Lee, James N; Marchand, William R

    2013-09-01

    Hyperkinetic perseveration (HKP) refers to perseverative repetition of rudimentary motor output. Although HKP is known to be associated with brain injuries and certain neurodegenerative disorders (primarily those involving the frontal lobes and the basal ganglia), an increased tendency to exhibit HKP is also commonly associated with apparently normal aging (i.e., in the absence of known neuropathology). The purpose of the present study was to examine anomalies in brain functioning associated with HKP tendencies in a non-injured brain. The present study examined functional MRI connectivity patterns associated with HKP in a sample of 24 "young" (ages 25-35 years) and 20 "old" (ages 65-75 years) healthy community dwelling women. Participants performed a motor learning task (the Push-Turn-Taptap task: PTT) known to elicit HKP. On a separate day, participants were scanned on a Siemens 3T Trio MR scanner with a 12-channel head coil, while performing a block-design motor sequence learning task that was designed to be a scanner analog for the PTT task. Cortico-subcortical connectivity patterns involving two subcortical regions of interest (putamen and thalamus) and three cortical regions (sensory-motor cortex, Brodmann Area 6, inferior frontal gyrus) were examined. Older participants exhibited a higher rate of HKP compared to younger participants. Age-related HKP was associated with hemispheric asymmetry marked by a relatively stronger right-hemisphere cortico-subcortical connectivity involving the sensory-motor cortex and, to a lesser extent, Brodmann Area 6. These patterns were distinct from connectivity patterns associated with aging alone. HKP is related to anomalies involving frontal-subcortical circuits. Future research should examine specific components of the basal-ganglia circuitry. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. 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

  8. 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.

  9. NeuN+ Neuronal Nuclei in Non-Human Primate Prefrontal Cortex and Subcortical White Matter After Clozapine Exposure

    PubMed Central

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

    2016-01-01

    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. PMID:26776227

  10. Speech and language disorders secondary to diffuse subcortical vascular lesions: Neurolinguistic and acoustic analysis. A case report.

    PubMed

    Tomić, Gordana; Stojanović, Milena; Pavlović, Aleksandra; Stanković, Predrag; Zidverc-Trajković, Jasna; Pavlović, Dragan; Marković-Jovanović, Zagorka; Covicković-Sternić, Nadezda

    2009-08-15

    Subcortical white matter (WM) plays an important role in speech production and language processing. Most frequently, cerebral WM lesions are secondary to small vessel disease in patients with vascular risk factors. We report the case of a 53-year-old man with history of hypertension and ischemic subcortical lesions, who presented with speech difficulties and mild cognitive impairment. Language and cognitive assessment included Boston Diagnostic Aphasia Examination, Boston Naming Test, Rey Auditory-Verbal Learning Test, Rey-Osterrieth Complex Figure Test, Trail Making Test A and B, Wisconsin Card Sorting Test, Scale for Evaluation of Perceptive Characteristics of Voice and Speech, and Multidimensional Evaluation of Speech and Voice. Brain MRI showed ischemic WM lesions and lacunar infarcts in the brainstem and right cerebellum. Cognitive testing revealed mild cognitive impairment, predominantly affecting attention and executive functions. Speech and language analysis demonstrated dysarthria, dysphonia with hypophonia, and imprecise articulation, as well as short rushes of speech, palilalia and mild subcortical dysphasia. Neurolinguistic and acoustic analysis in patients with ischemic WM lesions can provide additional information in the understanding of language and speech disturbances, and can assist in patient management.

  11. Parcellating an Individual Subject's Cortical and Subcortical Brain Structures Using Snowball Sampling of Resting-State Correlations

    PubMed Central

    Wig, Gagan S.; Laumann, Timothy O.; Cohen, Alexander L.; Power, Jonathan D.; Nelson, Steven M.; Glasser, Matthew F.; Miezin, Francis M.; Snyder, Abraham Z.; Schlaggar, Bradley L.; Petersen, Steven E.

    2014-01-01

    We describe methods for parcellating an individual subject's cortical and subcortical brain structures using resting-state functional correlations (RSFCs). Inspired by approaches from social network analysis, we first describe the application of snowball sampling on RSFC data (RSFC-Snowballing) to identify the centers of cortical areas, subdivisions of subcortical nuclei, and the cerebellum. RSFC-Snowballing parcellation is then compared with parcellation derived from identifying locations where RSFC maps exhibit abrupt transitions (RSFC-Boundary Mapping). RSFC-Snowballing and RSFC-Boundary Mapping largely complement one another, but also provide unique parcellation information; together, the methods identify independent entities with distinct functional correlations across many cortical and subcortical locations in the brain. RSFC parcellation is relatively reliable within a subject scanned across multiple days, and while the locations of many area centers and boundaries appear to exhibit considerable overlap across subjects, there is also cross-subject variability—reinforcing the motivation to parcellate brains at the level of individuals. Finally, examination of a large meta-analysis of task-evoked functional magnetic resonance imaging data reveals that area centers defined by task-evoked activity exhibit correspondence with area centers defined by RSFC-Snowballing. This observation provides important evidence for the ability of RSFC to parcellate broad expanses of an individual's brain into functionally meaningful units. PMID:23476025

  12. 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

  13. 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

  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. 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

  16. 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. © 2013 Elsevier

  17. 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

  18. 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

  19. 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.

  20. 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.

  1. The Prefrontal Cortex Achieves Inhibitory Control by Facilitating Subcortical Motor Pathway Connectivity

    PubMed Central

    Hughes, Laura E.; Anderson, Michael C.; Rowe, James B.

    2015-01-01

    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. PMID:25589771

  2. A cortical-subcortical syntax pathway linking Broca's area and the striatum.

    PubMed

    Teichmann, Marc; Rosso, Charlotte; Martini, Jean-Baptiste; Bloch, Isabelle; Brugières, Pierre; Duffau, Hugues; Lehéricy, Stéphane; Bachoud-Lévi, Anne-Catherine

    2015-06-01

    Combinatorial syntax has been shown to be underpinned by cortical key regions such as Broca's area and temporal cortices, and by subcortical structures such as the striatum. The cortical regions are connected via several cortico-to-cortical tracts impacting syntactic processing (e.g., the arcuate) but it remains unclear whether and how the striatum can be integrated into this cortex-centered syntax network. Here, we used a systematic stepwise approach to investigate the existence and syntactic function of an additional deep Broca-striatum pathway. We first asked 15 healthy controls and 12 patients with frontal/striatal lesions to perform three syntax tests. The results obtained were subjected to voxel-based lesion-symptom mapping (VLSM) to provide an anatomo-functional approximation of the pathway. The significant VLSM clusters were then overlapped with the probability maps of four cortico-cortical language tracts generated for 12 healthy participants (arcuate, extreme capsule fiber system, uncinate, aslant), including a probabilistic Broca-striatum tract. Finally, we carried out quantitative analyses of the relationship between the lesion load along the tracts and syntactic processing, by calculating tract-lesion overlap for each patient and analyzing the correlation with syntactic data. Our findings revealed a Broca-striatum tract linking BA45 with the left caudate head and overlapping with VLSM voxel clusters relating to complex syntax. The lesion load values for this tract were correlated with complex syntax scores, whereas no such correlation was observed for the other tracts. These results extend current syntax-network models, by adding a deep "Broca-caudate pathway," and are consistent with functional accounts of frontostriatal circuits. © 2015 Wiley Periodicals, Inc.

  3. Cortical and subcortical interactions during action reprogramming and their related white matter pathways

    PubMed Central

    Neubert, Franz-Xaver; Mars, Rogier B.; Buch, Ethan R.; Olivier, Etienne; Rushworth, Matthew F. S.

    2010-01-01

    The right inferior frontal gyrus (rIFG) and the presupplementary motor area (pre-SMA) have been identified with cognitive control—the top-down influence on other brain areas when nonroutine behavior is required. It has been argued that they “inhibit” habitual motor responses when environmental changes mean a different response should be made. However, whether such “inhibition” can be equated with inhibitory physiological interactions has been unclear, as has the areas’ relationship with each other and the anatomical routes by which they influence movement execution. Paired-pulse transcranial magnetic stimulation (ppTMS) was applied over rIFG and primary motor cortex (M1) or over pre-SMA and M1 to measure their interactions, at a subsecond scale, during either inhibition and reprogramming of actions or during routine action selection. Distinct patterns of functional interaction between pre-SMA and M1 and between rIFG and M1 were found that were specific to action reprogramming trials; at a physiological level, direct influences of pre-SMA and rIFG on M1 were predominantly facilitatory and inhibitory, respectively. In a subsequent experiment, it was shown that the rIFG's inhibitory influence was dependent on pre-SMA. A third experiment showed that pre-SMA and rIFG influenced M1 at two time scales. By regressing white matter fractional anisotropy from diffusion-weighted magnetic resonance images against TMS-measured functional connectivity, it was shown that short-latency (6 ms) and longer latency (12 ms) influences were mediated by cortico-cortical and subcortical pathways, respectively, with the latter passing close to the subthalamic nucleus. PMID:20622155

  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 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.

  6. Vertebrobasilar ectasia in patients with lacunar stroke: the secondary prevention of small subcortical strokes trial.

    PubMed

    Nakajima, Makoto; Pearce, Lesly A; Ohara, Nobuyuki; Field, Thalia S; Bazan, Carlos; Anderson, David C; Hart, Robert G; Benavente, Oscar R

    2015-05-01

    The clinical implications of vertebrobasilar ectasia (VBE) in patients with cerebral small-artery disease are not well defined. We investigated whether VBE is associated with recurrent stroke, major hemorrhage, and death in a large cohort of patients with recent lacunar stroke. Maximum diameters of the vertebral and basilar arteries were measured by magnetic resonance angiography and computed tomographic angiography in 2621 participants in the Secondary Prevention of Small Subcortical Strokes trial. VBE was defined a priori as basilar artery greater than 4.5 mm and/or vertebral artery greater than 4.0 mm. Patient characteristics and risks of stroke recurrence and mortality during follow-up (median, 3.5 years) were compared between patients with and without VBE. VBE affecting 1 or more arteries was present in 200 (7.6%) patients. Patient features independently associated with VBE were increasing age, male sex, white race ethnicity, hypertension, and higher baseline diastolic blood pressure. Baseline systolic blood pressure was inversely associated with VBE. After adjustment for other risk factors, VBE was not predictive of recurrent stroke (hazard ratio [HR], 1.3; 95% confidence interval [CI], .85-1.9) or major hemorrhage (HR, 1.5; CI, .94-2.6), but was of death (HR, 1.7; CI, 1.1-2.7). In this large well-characterized cohort of patients with recent lacunar stroke, VBE was predictive of death but not of recurrent stroke or major hemorrhage. In these exploratory analyses, the frequency of VBE was directly related to diastolic blood pressure but inversely related to systolic blood pressure. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  7. Motor and premotor cortices in subcortical stroke: proton magnetic resonance spectroscopy measures and arm motor impairment.

    PubMed

    Craciunas, Sorin C; Brooks, William M; Nudo, Randolph J; Popescu, Elena A; Choi, In-Young; Lee, Phil; Yeh, Hung-Wen; Savage, Cary R; Cirstea, Carmen M

    2013-06-01

    Although functional imaging and neurophysiological approaches reveal alterations in motor and premotor areas after stroke, insights into neurobiological events underlying these alterations are limited in human studies. We tested whether cerebral metabolites related to neuronal and glial compartments are altered in the hand representation in bilateral motor and premotor areas and correlated with distal and proximal arm motor impairment in hemiparetic persons. In 20 participants at >6 months postonset of a subcortical ischemic stroke and 16 age- and sex-matched healthy controls, the concentrations of N-acetylaspartate and myo-inositol were quantified by proton magnetic resonance spectroscopy. Regions of interest identified by functional magnetic resonance imaging included primary (M1), dorsal premotor (PMd), and supplementary (SMA) motor areas. Relationships between metabolite concentrations and distal (hand) and proximal (shoulder/elbow) motor impairment using Fugl-Meyer Upper Extremity (FMUE) subscores were explored. N-Acetylaspartate was lower in M1 (P = .04) and SMA (P = .004) and myo-inositol was higher in M1 (P = .003) and PMd (P = .03) in the injured (ipsilesional) hemisphere after stroke compared with the left hemisphere in controls. N-Acetylaspartate in ipsilesional M1 was positively correlated with hand FMUE subscores (P = .04). Significant positive correlations were also found between N-acetylaspartate in ipsilesional M1, PMd, and SMA and in contralesional M1 and shoulder/elbow FMUE subscores (P = .02, .01, .02, and .02, respectively). Our preliminary results demonstrated that proton magnetic resonance spectroscopy is a sensitive method to quantify relevant neuronal changes in spared motor cortex after stroke and consequently increase our knowledge of the factors leading from these changes to arm motor impairment.

  8. 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.

  9. Pathogenesis of cerebral microbleeds: In vivo imaging of amyloid and subcortical ischemic small vessel disease in 226 individuals with cognitive impairment.

    PubMed

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

    2013-05-01

    Cerebral microbleeds (CMBs) are a neuroimaging marker of small vessel disease (SVD) with relevance for understanding disease mechanisms in cerebrovascular disease, cognitive impairment, and normal aging. It is hypothesized that lobar CMBs are due to cerebral amyloid angiopathy (CAA) and deep CMBs are due to subcortical ischemic SVD. We tested this hypothesis using structural magnetic resonance imaging (MRI) markers of subcortical SVD and in vivo imaging of amyloid in patients with cognitive impairment. We included 226 patients: 89 with Alzheimer disease-related cognitive impairment (ADCI) and 137 with subcortical vascular cognitive impairment (SVCI). All subjects underwent amyloid imaging with [(11) C] Pittsburgh compound B (PiB) positron emission tomography, and MRI to detect CMBs and markers of subcortical SVD, including the volume of white matter hyperintensities (WMH) and the number of lacunes. Parietal and occipital lobar CMBs counts were higher in PiB(+) ADCI with moderate WMH than PiB(+) ADCI with minimal WMH, whereas PiB(-) patients with SVCI (ie, "pure" SVCI) showed both lobar and deep CMBs. In multivariate analyses of the whole cohort, WMH volume and lacuna counts were positively associated with both lobar and deep CMBs, whereas amyloid burden (PiB) was only associated with lobar CMBs. There was an interaction between lacuna burden and PiB retention on lobar (but not deep) CMBs (p<0.001). Our findings suggest that although deep CMBs are mainly linked to subcortical SVD, both subcortical SVD and amyloid-related pathologies (eg, CAA) contribute to the pathogenesis of lobar CMBs, at least in subjects with mixed lobar and deep CMBs. Furthermore, subcortical SVD and amyloid-related pathologies interact to increase the risk of lobar CMBs. Copyright © 2012 American Neurological Association.

  10. 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.

  11. Subcortical hematoma caused by cerebral amyloid angiopathy: does the first evidence of hemorrhage occur in the subarachnoid space?

    PubMed

    Takeda, Shigeki; Yamazaki, Kazunori; Miyakawa, Teruo; Onda, Kiyoshi; Hinokuma, Kaoru; Ikuta, Fusahiro; Arai, Hiroyuki

    2003-12-01

    Six autopsy cases of subcortical hematoma caused by CAA were examined to elucidate the primary site of hemorrhage. Immunohistochemistry for amyloid beta-protein (A beta) revealed extensive CAA in the intrasulcal meningeal vessels rather than in the cerebral cortical vessels. All of the examined cases had multiple hematomas in the subarachnoid space, mainly in the cerebral sulci, as well as intracerebral hematomas. Each intracerebral hematoma was connected to the subarachnoid hematomas at the depth of cerebral sulci or through the lateral side of the cortex. There was no debris of the cerebral cortical tissue in the subarachnoid hematomas. In case 2, another solitary subarachnoid hematoma, which was not connected to any intracerebral hematoma, was seen. In all of these subarachnoid hematomas, many ruptured A beta-immunopositive arteries were observed. These ruptured arteries did not accompany any debris of the brain tissue, some of them were large in diameter (250-300 microm), and several of them were far from the cerebral cortex. Therefore, it was considered that they were not cortical arteries but meningeal arteries. Within the cerebral cortex, there were only a few ruptured arteries associated with small hemorrhages. There were no ruptured vessels within the intracerebral hematomas. There was a strong suggestion that all of the subarachnoid hematomas, including the solitary one in case 2, originated from the rupture of the meningeal arteries. The present study indicates that in some cases of subcortical hematoma caused by CAA, the primary hemorrhage occurs in the subarachnoid space, in particular the cerebral sulci, because of rupture of multiple meningeal arteries. Infarction occurs subsequently in the cortex around the hematoma, the hematoma penetrates into the brain parenchyma, and finally, a subcortical hematoma is formed.

  12. Impairment of visuospatial/visuoconstructional skills in multiple sclerosis patients: the correlation with regional lesion load and subcortical atrophy.

    PubMed

    Marasescu, R; Cerezo Garcia, M; Aladro Benito, Y

    2016-04-01

    About 20% to 26% of patients with multiple sclerosis (MS) show alterations in visuospatial/visuoconstructive (VS-VC) skills even though temporo-parieto-occipital impairment is a frequent finding in magnetic resonance imaging. No studies have specifically analysed the relationship between these functions and lesion volume (LV) in these specific brain areas. To evaluate the relationship between VS-VC impairment and magnetic resonance imaging temporo-parieto-occipital LV with subcortical atrophy in patients with MS. Of 100 MS patients undergoing a routine neuropsychological evaluation, 21 were selected because they displayed VS-VC impairments in the following tests: Incomplete picture, Block design (WAIS-III), and Rey-Osterrieth complex figure test. We also selected 13 MS patients without cognitive impairment (control group). Regional LV was measured in FLAIR and T1-weighted images using a semiautomated method; subcortical atrophy was measured by bicaudate ratio and third ventricle width. Partial correlations (controlling for age and years of school) and linear regression analysis were employed to analyse correlations between magnetic resonance imaging parameters and cognitive performance. All measures of LV and brain atrophy were significantly higher in patients with cognitive impairment. Regional LV, bicaudate ratio, and third ventricle width are significantly and inversely correlated with cognitive performance; the strongest correlation was between third ventricle width and VC performance (Block design: P=.001; Rey-Osterrieth complex figure: P<.000). In the multivariate analysis, third ventricle width only had a significant effect on performance of VC tasks (Block design: P=.000; Rey-Osterrieth complex figure: P=.000), and regional FLAIR VL was linked to the VS task (Incomplete picture; P=.002). Measures of subcortical atrophy explain the variations in performance on visuocostructive tasks, and regional FLAIR VL measures are linked to VS tasks. Copyright © 2015

  13. Exploring the effects of coexisting amyloid in subcortical vascular cognitive impairment.

    PubMed

    Dao, Elizabeth; Hsiung, Ging-Yuek Robin; Sossi, Vesna; Jacova, Claudia; Tam, Roger; Dinelle, Katie; Best, John R; Liu-Ambrose, Teresa

    2015-10-12

    Mixed pathology, particularly Alzheimer's disease with cerebrovascular lesions, is reported as the second most common cause of dementia. Research on mixed dementia typically includes people with a primary AD diagnosis and hence, little is known about the effects of co-existing amyloid pathology in people with vascular cognitive impairment (VCI). The purpose of this study was to understand whether individual differences in amyloid pathology might explain variations in cognitive impairment among individuals with clinical subcortical VCI (SVCI). Twenty-two participants with SVCI completed an (11)C Pittsburgh compound B (PIB) position emission tomography (PET) scan to quantify global amyloid deposition. Cognitive function was measured using: 1) MOCA; 2) ADAS-Cog; 3) EXIT-25; and 4) specific executive processes including a) Digits Forward and Backwards Test, b) Stroop-Colour Word Test, and c) Trail Making Test. To assess the effect of amyloid deposition on cognitive function we conducted Pearson bivariate correlations to determine which cognitive measures to include in our regression models. Cognitive variables that were significantly correlated with PIB retention values were entered in a hierarchical multiple linear regression analysis to determine the unique effect of amyloid on cognitive function. We controlled for age, education, and ApoE ε4 status. Bivariate correlation results showed that PIB binding was significantly correlated with ADAS-Cog (p < 0.01) and MOCA (p < 0.01); increased PIB binding was associated with worse cognitive function on both cognitive measures. PIB binding was not significantly correlated with the EXIT-25 or with specific executive processes (p > 0.05). Regression analyses controlling for age, education, and ApoE ε4 status indicated an independent association between PIB retention and the ADAS-Cog (adjusted R-square change of 15.0%, Sig F Change = 0.03). PIB retention was also independently associated with MOCA scores (adjusted R

  14. Microbleeds in the Secondary Prevention of Small Subcortical Strokes Trial: Stroke, mortality, and treatment interactions.

    PubMed

    Shoamanesh, Ashkan; Pearce, Lesly A; Bazan, Carlos; Catanese, Luciana; McClure, Leslie A; Sharma, Mukul; Marti-Fabregas, Joan; Anderson, David C; Kase, Carlos S; Hart, Robert G; Benavente, Oscar R

    2017-08-01

    To characterize cerebral microbleeds (CMBs) in lacunar stroke patients in the Secondary Prevention of Small Subcortical Strokes (SPS3) trial and to assess their relationship with recurrent stroke and death, and response to assigned treatment. SPS3 is a randomized, clinical trial conducted between 2003 and 2011. Patients with recent magnetic resonance imaging (MRI)-documented lacunar infarcts were randomly assigned in a factorial design to target levels of systolic blood pressure (130-149mmHg vs <130mmHg; open label) and to antiplatelet treatment (aspirin/clopidogrel vs aspirin/placebo; double-blinded). The current analysis involves 1,278 trial participants who had a baseline axial T2*-weighted gradient echo MRI sequence allowing for CMB detection. CMBs were present in 30% of 1,278 patients (mean age = 63 years). Male gender (odds ratio [OR] = 1.7, 95% confidence interval [CI] = 1.3-2.3), history of hypertension (OR = 1.6, 95% CI = 1.2-2.3), increased systolic blood pressure (1.2 per 20mmHg, 95% CI = 1.1-1.4), nondiabetic status (OR = 1.4, 95% CI = 1.1-1.9), multiple old lacunar infarcts (OR = 1.9, 95% CI = 1.5-2.5), and moderate (OR = 1.7, 95% CI = 1.2-2.3) or severe (OR = 4.2, 95% CI = 3.0-5.9) white matter hyperintensities on MRI were independently associated with CMBs. During a mean follow-up of 3.3 years, overall stroke recurrence was 2.5% per patient-year. Patients with CMBs had an adjusted 2-fold increased risk of recurrent stroke (hazard ratio = 2.1, 95% CI = 1.4-3.1). CMBs were not a risk factor for death. There were no statistically significant interactions between CMBs and treatment assignments. Patients with lacunar stroke and CMBs likely harbor a more advanced form of cerebral small vessel disease in need of efficacious therapeutic strategies. Ann Neurol 2017;82:196-207. © 2017 American Neurological Association.

  15. 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

  16. 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.

  17. 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.

  18. Simultaneously-evoked auditory potentials (SEAP): A new method for concurrent measurement of cortical and subcortical auditory-evoked activity.

    PubMed

    Slugocki, Christopher; Bosnyak, Daniel; Trainor, Laurel J

    2017-03-01

    Recent electrophysiological work has evinced a capacity for plasticity in subcortical auditory nuclei in human listeners. Similar plastic effects have been measured in cortically-generated auditory potentials but it is unclear how the two interact. Here we present Simultaneously-Evoked Auditory Potentials (SEAP), a method designed to concurrently elicit electrophysiological brain potentials from inferior colliculus, thalamus, and primary and secondary auditory cortices. Twenty-six normal-hearing adult subjects (mean 19.26 years, 9 male) were exposed to 2400 monaural (right-ear) presentations of a specially-designed stimulus which consisted of a pure-tone carrier (500 or 600 Hz) that had been amplitude-modulated at the sum of 37 and 81 Hz (depth 100%). Presentation followed an oddball paradigm wherein the pure-tone carrier was set to 500 Hz for 85% of presentations and pseudo-randomly changed to 600 Hz for the remaining 15% of presentations. Single-channel electroencephalographic data were recorded from each subject using a vertical montage referenced to the right earlobe. We show that SEAP elicits a 500 Hz frequency-following response (FFR; generated in inferior colliculus), 80 (subcortical) and 40 (primary auditory cortex) Hz auditory steady-state responses (ASSRs), mismatch negativity (MMN) and P3a (when there is an occasional change in carrier frequency; secondary auditory cortex) in addition to the obligatory N1-P2 complex (secondary auditory cortex). Analyses showed that subcortical and cortical processes are linked as (i) the latency of the FFR predicts the phase delay of the 40 Hz steady-state response, (ii) the phase delays of the 40 and 80 Hz steady-state responses are correlated, and (iii) the fidelity of the FFR predicts the latency of the N1 component. The SEAP method offers a new approach for measuring the dynamic encoding of acoustic features at multiple levels of the auditory pathway. As such, SEAP is a promising tool with which to study how

  19. 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.

  20. Acute encephalopathy with biphasic seizures and late reduced diffusion

    PubMed Central

    Yadav, Saroj S.; Lawande, Malini A.; Kulkarni, Shilpa D.; Patkar, Deepak A.

    2013-01-01

    Acute encephalopathy with biphasic seizures and reduced diffusion (AESD) is a syndrome of encephalopathy characterized by biphasic seizures and altered consciousness in the acute stage followed in the subacute stage by restricted diffusion in the subcortical white matter on magnetic resonance imaging. The etiology of AESD has been attributed to viral infection like influenza A and human herpes virus 6. The exact pathogenesis of AESD is uncertain. Here we report a case of AESD, diagnosed based on clinicoradiological correlation. PMID:23772250

  1. Cholinergic subcortical hyperintensities in Alzheimer's disease patients from the Sunnybrook Dementia Study: relationships with cognitive dysfunction and hippocampal atrophy.

    PubMed

    McNeely, Alicia A; Ramirez, Joel; Nestor, Sean M; Zhao, Jiali; Gao, Fuqiang; Kiss, Alex; Stuss, Donald T; Black, Sandra E

    2015-01-01

    Subcortical hyperintensities within the cholinergic fiber projections (chSH) on MRI are believed to reflect cerebral small vessel disease (SVD) which may adversely impact cognition. Additionally, hippocampal atrophy represents a commonly used biomarker to support the diagnosis of Alzheimer's disease (AD). To examine potential differences in neuropsychological test performance between AD patients (n = 234) with high and low chSH volumes and whether these differences corresponded to hippocampal atrophy. A modified version of Lesion Explorer was used to volumetrically quantify chSH severity. The Sunnybrook Hippocampal Volumetry Tool was applied to obtain hippocampal volumes. Composite z-scores to assess executive, memory, and visuospatial functioning were generated from standardized neuropsychological test performance scores. Inter-method technique validation demonstrated a high degree of correspondence with the Cholinergic Pathways Hyperintensities Scale (n = 40, ρ = 0.84, p < 0.001). After adjusting for brain atrophy, disease severity, global SH volumes, and demographic variables, multivariate analyses revealed a significant group difference, with the high chSH group demonstrating poorer memory function compared to the low chSH group (p = 0.03). A significant difference was found between low and high chSH groups in total (p < 0.05) and left (p < 0.01) hippocampal volume. These results suggest degradation of the cholinergic projections due to strategic SVD may independently contribute to memory dysfunction and hippocampal atrophy. Future studies examining subcortical vasculopathy in the cholinergic pathways may have implications on the development of therapeutic strategies for dementia and SVD.

  2. Functions of gamma-band synchronization in cognition: from single circuits to functional diversity across cortical and subcortical systems.

    PubMed

    Bosman, Conrado A; Lansink, Carien S; Pennartz, Cyriel M A

    2014-06-01

    Gamma-band activity (30-90 Hz) and the synchronization of neural activity in the gamma-frequency range have been observed in different cortical and subcortical structures and have been associated with different cognitive functions. However, it is still unknown whether gamma-band synchronization subserves a single universal function or a diversity of functions across the full spectrum of cognitive processes. Here, we address this question reviewing the mechanisms of gamma-band oscillation generation and the functions associated with gamma-band activity across several cortical and subcortical structures. Additionally, we raise a plausible explanation of why gamma rhythms are found so ubiquitously across brain structures. Gamma band activity originates from the interplay between inhibition and excitation. We stress that gamma oscillations, associated with this interplay, originate from basic functional motifs that conferred advantages for low-level system processing and multiple cognitive functions throughout evolution. We illustrate the multifunctionality of gamma-band activity by considering its role in neural systems for perception, selective attention, memory, motivation and behavioral control. We conclude that gamma-band oscillations support multiple cognitive processes, rather than a single one, which, however, can be traced back to a limited set of circuit motifs which are found universally across species and brain structures. © 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  3. Assessing cortical and subcortical changes in a western diet mouse model using spectral/Fourier domain OCT (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Bernucci, Marcel T.; Norman, Jennifer E.; Merkle, Conrad W.; Aung, Hnin H.; Rutkowsky, Jennifer; Rutledge, John C.; Srinivasan, Vivek J.

    2017-02-01

    The Western diet, causative in the development of atherosclerotic cardiovascular disease, has recently been associated with the development of diffuse white matter disease (WMD) and other subcortical changes. Yet, little is known about the pathophysiological mechanisms by which a high-fat diet can cause WMD. Mechanistic studies of deep brain regions in mice have been challenging due to a lack of non-invasive, high-resolution, and deep imaging technologies. Here we used Optical Coherence Tomography to study mouse cortical/subcortical structures noninvasively and in vivo. To better understand the role of Western Diet in the development of WMD, intensity and Doppler flow OCT images, obtained using a 1300 nm spectral / Fourier domain OCT system, were used to observe the structural and functional alterations in the cortex and corpus callosum of Western Diet and control diet mouse models. Specifically, we applied segmentation to the OCT images to identify the boundaries of the cortex/corpus callosum, and further quantify the layer thicknesses across animals between the two diet groups. Furthermore, microvasculature alterations such as changes in spatiotemporal flow profiles within diving arterioles, arteriole diameter, and collateral tortuosity were analyzed. In the current study, while the arteriole vessel diameters between the two diet groups was comparable, we show that collateral tortuosity was significantly higher in the Western diet group, compared to control diet group, possibly indicating remodeling of brain vasculature due to dietary changes. Moreover, there is evidence showing that the corpus callosum is thinner in Western diet mice, indicative of tissue atrophy.

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

    PubMed

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

    2013-03-01

    This research examines the relationship between brain activity recorded with functional magnetic resonance imaging (fMRI) and event related potentials (ERP) as these responses varied over a series of emotionally evocative and neutral pictures. We investigate the relationship of early occipitotemporal and later centroparietal emotion-modulated ERPs in one sample to 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 neural 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. Copyright © 2012 Elsevier B.V. All rights reserved.

  5. 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.

  6. (18)F-AV-1451 binds to motor-related subcortical gray and white matter in corticobasal syndrome.

    PubMed

    Cho, Hanna; Baek, Min Seok; Choi, Jae Yong; Lee, Seung Ha; Kim, Joong Seok; Ryu, Young Hoon; Lee, Myung Sik; Lyoo, Chul Hyoung

    2017-09-12

    To investigate tau distribution in patients with corticobasal syndrome (CBS) using (18)F-AV-1451 PET. Six consecutively recruited patients with CBS and 20 age-matched healthy controls underwent 2 PET scans with (18)F-AV-1451 (for tau) and (18)F-florbetaben (for β-amyloid). We compared standardized uptake value ratio maps of the (18)F-AV-1451 PET images between the patients with CBS and controls. Compared to controls, patients with CBS exhibited asymmetrically increased (18)F-AV-1451 binding in the putamen, globus pallidus, and thalamus contralateral to the clinically more affected side and in the ipsilateral globus pallidus and dentate nucleus. Voxel-based comparison additionally showed asymmetrically increased (18)F-AV-1451 binding in the focal regions of the precentral gray and white matter and in the midbrain, predominantly in the contralateral side. (18)F-AV-1451 binding in the precentral white matter correlated with motor severity. (18)F-AV-1451 asymmetrically binds to motor-related subcortical gray and white matter structures in patients with CBS. This pattern corresponds to tau pathology distribution in postmortem studies, and motor deficit in patients with CBS may be associated with tau accumulation predominantly in the subcortical white matter underlying the motor cortex, leading to disruptions in motor-related networks. © 2017 American Academy of Neurology.

  7. FreeSurfer-Initiated Fully-Automated Subcortical Brain Segmentation in MRI Using Large Deformation Diffeomorphic Metric Mapping

    PubMed Central

    Khan, Ali R.; Wang, Lei

    2010-01-01

    Fully-automated brain segmentation methods have not been widely adopted for clinical use because of issues related to reliability, accuracy, and limitations of delineation protocol. By combining the probabilistic-based FreeSurfer (FS) method with the Large Deformation Diffeomorphic Metric Mapping (LDDMM) based label propagation method, we are able to increase reliability and accuracy, and allow for flexibility in template choice. Our method uses the automated FreeSurfer subcortical labeling to provide a coarse to fine introduction of information in the LDDMM template-based segmentation resulting in a fully-automated subcortical brain segmentation method (FS+LDDMM). One major advantage of the FS+LDDMM-based approach is that the automatically generated segmentations generated are inherently smooth, thus subsequent steps in shape analysis can directly follow without manual post-processing or loss of detail. We have evaluated our new FS+LDDMM method on several databases containing a total of 50 subjects with different pathologies, scan sequences and manual delineation protocols for labeling the basal ganglia, thalamus, and hippocampus. In healthy controls we report Dice overlap measures of 0.81, 0.83, 0.74, 0.86 and 0.75 for the right caudate nucleus, putamen, pallidum, thalamus and hippocampus respectively. We also find statistically significant improvement of accuracy in FS+LDDMM over FreeSurfer for the caudate nucleus and putamen of Huntington’s disease and Tourette’s syndrome subjects, and the right hippocampus of Schizophrenia subjects. PMID:18455931

  8. 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

  9. 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

  10. The Relationship between Cortical Blood Flow and Sub-Cortical White-Matter Health across the Adult Age Span

    PubMed Central

    Chen, J. Jean; Rosas, H. Diana; Salat, David H.

    2013-01-01

    Degeneration of cerebral white matter is commonly observed in aging, and the associated degradation in neural connectivity contributes to cognitive decline in older adults. Vascular dysfunction has been implicated as a potential mechanism for general age-related neural tissue deterioration; however, no prior study has examined the direct relationship between cortical vascular health and subcortical white-matter integrity. In this work, we aimed to determine whether blood supply to the brain is associated with microstructural integrity of connective tissue, and whether such associations are regionally specific and mainly accounted for by aging. We examined the association between cerebral blood flow (CBF) in the cortical mantle, measured using arterial spin labeling (ASL), and subcortical white-matter integrity, measured using diffusion tensor imaging (DTI), in a group of healthy adults spanning early to late adulthood. We found cortical CBF to be significantly associated with white-matter integrity throughout the brain. In addition, these associations were only partially tied to aging, as they remained even when statistically controlling for age, and when restricting the analyses to a young subset of the sample. Furthermore, vascular risk was not a prominent determinant of these effects. These findings suggest that the overall blood supply to the brain is an important indicator of white-matter health in the normal range of variations amongst adults, and that the decline in CBF with advancing age may potentially exacerbate deterioration of the connective anatomy of the brain. PMID:23437228

  11. 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.

  12. [Effect of brain atrophy on the cognition in patients with subcortical ischemic vascular disease].

    PubMed

    Tong, X X; Wang, L; Zhou, X; Zhang, C; Fang, L; Zhou, Y J; Sun, Z W

    2016-01-05

    To explore the effect of brain atrophy on the cognition in patients with subcortical ischemic vascular disease (SIVD). A total of 116 SIVD patients were enrolled from the Department of Neurology, First Affiliated Hospital, Anhui Medical University between September 2013 and December 2014. Lobar atrophy, leukoaraiosis (LA), lacunar infarcts (LI) and vascular risk factors were analyzed in the 116 SIVD patients who were divided into three groups according to the diagnostic criteria: non-cognitive impairment group (SIVD-NCI) , mild cognitive impairment group (SIVD-MCI) and dement group (SIVD-VaD). All patients underwent magnetic resonance imaging (MRI) with a 3.0-T system. The cognitive functions were evaluated by mini-metal state examination (MMSE), the Cambridge cognitive examination-Chinese version (CAMCOG-C), etc. A widely used visual atrophy rating method (0 to 3) was adopted to rate the severity of frontal, parietal and temporal lobe atrophy. The degree of LA and the numbers of LI in 4 brain regions (frontal, parieto-occipital, temporal, and basal ganglia) were evaluated meanwhile. Firstly, both the SIVD-MCI and SIVD-VaD groups showed significantly higher total scores of atrophy, higher frontal lobe atrophy scores, higher LA scores and larger LI numbers than SIVD-NCI (H=6.138, P=0.013; H=45.845, P=0.000; H=36.818, P=0.000; H=37.46, P=0.000). There were no significant differences in temporal lobe atrophy scores between SIVD-NCI group and SIVD-MCI group. Parietal lobe atrophy scores also showed no differences among the three groups. Secondly, as well as total numbers of LI, total scores of atrophy and LA were negatively correlated with SIVD cognition, especially frontal lobe atrophy scores, parieto-occipital LA scores and basal ganglia LI numbers had a remarkable negative correlation with MMSE scores, CAMCOG-C scores and partial subitems in CAMCOG-C scores (P<0.005). However temporal LI numbers was absence of correlation with MMSE scores, CAMCOG-C scores and

  13. Intraoperative use of diffusion tensor imaging-based tractography for resection of gliomas located near the pyramidal tract: comparison with subcortical stimulation mapping and contribution to surgical outcomes.

    PubMed

    Vassal, F; Schneider, F; Nuti, C

    2013-10-01

    For gliomas, the goal of surgery is maximal tumour removal with the preservation of neurological function. We evaluated the contribution of the combination of diffusion tensor imaging-based fibre tracking (DTI-FT) of the pyramidal tract (PT) integrated to the navigation and subcortical direct electrical stimulations (DESs) to surgical outcomes. Ten patients underwent surgery for gliomas located in close relationship with the subcortical course of the PT. Preoperative DTI was performed with a three-Tesla magnetic resonance scanner applying an echo-planar sequence with 20 diffusion directions. DTI-FT data were systematically loaded into the navigation for intraoperative guidance. When the resection closely approached the PT as illustrated on navigation images, subcortical DESs were used to confirm the proximity of the PT by observing motor responses. The location of all subcortically stimulated points with positive motor response was correlated with the illustrated PT. Motor deficits were evaluated pre- and postoperatively, and compared with the extent of tumour removal. DTI-FT of the PT was successfully performed in all patients. A total of fifteen positive subcortical DESs were obtained in 8 of 10 patients; in these cases, the mean distance from the stimulated point to the PT was 6.2 ± 3.6 mm. The mean tumoural volumetric resection was 90.8 ± 10.4%, with a gross total resection in four patients. At one month after surgery, only one patient had a slight impairment of motor function (decreased fine motor hand skills). DTI-FT is an accurate technique to map the PT in the vicinity of brain tumours. By combining anatomical (DTI-FT) and functional (subcortical DES) studies for intraoperative localization of the PT, the authors achieved a good volumetric resection of tumours located in eloquent motor areas, with low morbidity. Careful use of this protocol requires the knowledge of some pitfalls, mainly the occurrence of brain shift during removal of large tumours.

  14. 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

  15. 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

  16. 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

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

    PubMed

    Brookes, Rebecca L; Hollocks, Matthew J; Tan, Rhea Y Y; Morris, Robin G; Markus, Hugh S

    2016-10-01

    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. 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. 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. The results indicate that the BMET and the MoCA are clinically useful and sensitive screening measures for early cognitive impairment in patients with CADASIL. © 2016 The Authors.

  18. 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

  19. 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.

  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. 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.

  2. Patient with rapidly evolving neurological disease with neuropathological lesions of Creutzfeldt-Jakob disease, Lewy body dementia, chronic subcortical vascular encephalopathy and meningothelial meningioma.

    PubMed

    Vita, Maria Gabriella; Tiple, Dorina; Bizzarro, Alessandra; Ladogana, Anna; Colaizzo, Elisa; Capellari, Sabina; Rossi, Marcello; Parchi, Piero; Masullo, Carlo; Pocchiari, Maurizio

    2017-04-01

    We report a case of rapidly evolving neurological disease in a patient with neuropathological lesions of Creutzfeldt-Jakob disease (CJD), Lewy body dementia (LBD), chronic subcortical vascular encephalopathy and meningothelial meningioma. The coexistence of severe multiple pathologies in a single patient strengthens the need to perform accurate clinical differential diagnoses in rapidly progressive dementias. © 2016 Japanese Society of Neuropathology.

  3. Anti-N-methyl-D-aspartate receptor encephalitis concomitant with multifocal subcortical white matter lesions on magnetic resonance imaging: a case report and review of the literature.

    PubMed

    Wang, Rui-Jin; Chen, Bu-Dong; Qi, Dong

    2015-07-08

    Anti-N-methyl-D-aspartate receptor encephalitis is a severe autoimmune disorder characterized by severe psychiatric symptoms, seizures, decreased consciousness, autonomic dysregulation, and dyskinesias. Multifocal subcortical white matter lesions on fluid-attenuated inversion recovery and diffuse weighted images have rarely been reported in previous literature, and serial magnetic resonance imaging changes after plasma exchange have not been presented before. A previously healthy 24-year-old Chinese woman presented with acute psychiatric symptoms characterized by fear and agitation followed by decreased consciousness, dyskinesias, and seizures. Magnetic resonance imaging revealed hyperintense lesions on fluid-attenuated inversion recovery and diffuse weighted images in bilateral subcortical white matter. Cerebrospinal fluid analysis revealed a mild pleocytosis with lymphocytic predominance. Protein and glucose levels were normal. Aquaporin-4 antibodies in serum and cerebrospinal fluid were negative. Identification of anti-N-methyl-D-aspartate receptor antibodies in serum and cerebrospinal fluid confirmed the diagnosis of anti-N-methyl-D-aspartate receptor encephalitis. She was initially treated with combined intravenous immunoglobulin and methylprednisolone without improvement. Plasma exchange was then initiated with good response; the patient made a full recovery after several cycles of plasma exchange. Repeat magnetic resonance imaging performed 1 month after plasma exchange showed partial resolution of the hyperintense lesions in bilateral subcortical white matter, and follow-up magnetic resonance imaging 2 months after plasma exchange showed complete resolution. Anti-N-methyl-D-aspartate receptor encephalitis may be concomitant with multifocal subcortical white matter lesions. Such lesions may resolve after appropriate immunotherapy.

  4. 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

  5. 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.

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

    PubMed

    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.

  7. 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.

  8. 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

  9. 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

  10. Cortical and subcortical connectivity changes during decreasing levels of consciousness in humans: a functional magnetic resonance imaging study using propofol.

    PubMed

    Mhuircheartaigh, Róisín Ní; Rosenorn-Lanng, Debbie; Wise, Richard; Jbabdi, Saad; Rogers, Richard; Tracey, Irene

    2010-07-07

    While ubiquitous, pharmacological manipulation of consciousness remains poorly defined and incompletely understood (Prys-Roberts, 1987). This retards anesthetic drug development, confounds interpretation of animal studies conducted under anesthesia, and limits the sensitivity of clinical monitors of cerebral function to intact perception. Animal and human studies propose a functional "switch" at the level of the thalamus, with inhibition of thalamo-cortical transmission characterizing loss of consciousness (Alkire et al., 2000; Mashour, 2006). We investigated the effects of propofol, widely used for anesthesia and sedation, on spontaneous and evoked cerebral activity using functional magnetic resonance imaging (fMRI). A series of auditory and noxious stimuli was presented to eight healthy volunteers at three behavioral states: awake, "sedated" and "unresponsive." Performance in a verbal task and the absence of a response to verbal stimulation, rather than propofol concentrations, were used to define these states clinically. Analysis of stimulus-related blood oxygenation level-dependent signal changes identified reductions in cortical and subcortical responses to auditory and noxious stimuli in sedated and unresponsive states. A specific reduction in activity within the putamen was noted and further investigated with functional connectivity analysis. Progressive failure to perceive or respond to auditory or noxious stimuli was associated with a reduction in the functional connectivity between the putamen and other brain regions, while thalamo-cortical connectivity was relatively preserved. This result has not been previously described and suggests that disruption of subcortical thalamo-regulatory systems may occur before, or even precipitate, failure of thalamo-cortical transmission with the induction of unconsciousness.

  11. Measurement of Cortical Thickness and Volume of Subcortical Structures in Multiple Sclerosis: Agreement between 2D Spin-Echo and 3D MPRAGE T1-Weighted Images.

    PubMed

    Vidal-Jordana, A; Pareto, D; Sastre-Garriga, J; Auger, C; Ciampi, E; Montalban, X; Rovira, A

    2017-02-01

    Gray matter pathology is known to occur in multiple sclerosis and is related to disease outcomes. FreeSurfer and the FMRIB Integrated Registration and Segmentation Tool (FIRST) have been developed for measuring cortical and subcortical gray matter in 3D-gradient-echo T1-weighted images. Unfortunately, most historical MS cohorts do not have 3D-gradient-echo, but 2D-spin-echo images instead. We aimed to evaluate whether cortical thickness and the volume of subcortical structures measured with FreeSurfer and FIRST could be reliably measured in 2D-spin-echo images and to investigate the strength and direction of clinicoradiologic correlations. Thirty-eight patients with MS and 2D-spin-echo and 3D-gradient-echo T1-weighted images obtained at the same time were analyzed by using FreeSurfer and FIRST. The intraclass correlation coefficient between the estimates was obtained. Correlation coefficients were used to investigate clinicoradiologic associations. Subcortical volumes obtained with both FreeSurfer and FIRST showed good agreement between 2D-spin-echo and 3D-gradient-echo images, with 68.8%-76.2% of the structures having either a substantial or almost perfect agreement. Nevertheless, with FIRST with 2D-spin-echo, 18% of patients had mis-segmentation. Cortical thickness had the lowest intraclass correlation coefficient values, with only 1 structure (1.4%) having substantial agreement. Disease duration and the Expanded Disability Status Scale showed a moderate correlation with most of the subcortical structures measured with 3D-gradient-echo images, but some correlations lost significance with 2D-spin-echo images, especially with FIRST. Cortical thickness estimates with FreeSurfer on 2D-spin-echo images are inaccurate. Subcortical volume estimates obtained with FreeSurfer and FIRST on 2D-spin-echo images seem to be reliable, with acceptable clinicoradiologic correlations for FreeSurfer. © 2017 by American Journal of Neuroradiology.

  12. Cortical and Subcortical Grey and White Matter Atrophy in Myotonic Dystrophies Type 1 and 2 Is Associated with Cognitive Impairment, Depression and Daytime Sleepiness

    PubMed Central

    Prehn, Christian; Krogias, Christos; Schneider, Ruth; Klein, Jan; Gold, Ralf; Lukas, Carsten

    2015-01-01

    Objectives Central nervous system involvement is one important clinical aspect of myotonic dystrophy type 1 and 2 (DM1 and DM2). We assessed CNS involvement DM1 and DM2 by 3T MRI and correlated clinical and neuocognitive symptoms with brain volumetry and voxel-based morphometry (VBM). Methods 12 patients with juvenile or classical DM1 and 16 adult DM2 patients underwent 3T MRI, a thorough neurological and neuropsychological examination and scoring of depression and daytime sleepiness. Volumes of brain, ventricles, cerebellum, brainstem, cervical cord, lesion load and VBM results of the patient groups were compared to 33 matched healthy subjects. Results Clinical symptoms were depression (more pronounced in DM2), excessive daytime sleepiness (more pronounced in DM1), reduced attention and flexibility of thinking, and deficits of short-term memory and visuo-spatial abilities in both patient groups. Both groups showed ventricular enlargement and supratentorial GM and WM atrophy, with prevalence for more GM atrophy and involvement of the motor system in DM1 and more WM reduction and affection of limbic structures in DM2. White matter was reduced in DM1 in the splenium of the corpus callosum and in left-hemispheric WM adjacent to the pre- and post-central gyrus. In DM2, the bilateral cingulate gyrus and subgyral medio-frontal and primary somato-sensory WM was affected. Significant structural-functional correlations of morphological MRI findings (global volumetry and VBM) with clinical findings were found for reduced flexibility of thinking and atrophy of the left secondary visual cortex in DM1 and of distinct subcortical brain structures in D