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1.  Blocking estradiol synthesis affects memory for songs in auditory forebrain of male zebra finches 
Neuroreport  2012;23(16):922-926.
Estradiol (E2) has recently been shown to modulate sensory processing in an auditory area of the songbird forebrain, the caudomedial nidopallium (NCM). When a bird hears conspecific song, E2 increases locally in NCM, where neurons express both the aromatase enzyme that synthesizes E2 from precursors and estrogen receptors. Auditory responses in NCM show a form of neuronal memory: repeated playback of the unique learned vocalizations of conspecific individuals induces long-lasting stimulus specific adaptation (SSA) of neural responses to each vocalization. In order to test the role of E2 in this auditory memory, we treated adult male zebra finches (n=16) with either the aromatase inhibitor Fadrozole (FAD) or saline for 8 days. We then exposed them to “training” songs and, 6h later, recorded multiunit auditory responses with an array of 16 microelectrodes in NCM. Adaptation rates (a measure of SSA) to playbacks of training and novel songs were computed, using established methods, to provide a measure of neuronal memory. Recordings from FAD-treated birds showed significantly reduced memory for the training songs compared to saline-treated controls, while auditory processing for novel songs did not differ between treatment groups. In addition, FAD did not change the response bias in favor of conspecific over heterospecific song stimuli. Our results show that E2 depletion affects the neuronal memory for vocalizations in songbird NCM, and suggest that E2 plays a necessary role in auditory processing and memory for communication signals.
PMCID: PMC4322868  PMID: 22955141
songbirds; NCM; auditory processing; estradiol; memory; stimulus specific adaptation; animal vocalization; species specificity
2.  Age-related differences in the automatic processing of single letters: implications for selective attention 
Neuroreport  2014;25(2):77-82.
Older adults exhibit diminished ability to inhibit the processing of visual stimuli that are supposed to be ignored. The extent to which age-related changes in early visual processing contribute to impairments in selective attention remains to be determined. Here, 103 adults, ages 18-85, completed a color selective attention task in which they were asked to attend to a specified color and respond to designated target letters. An optimal approach would be to initially filter according to color and then process letter forms in the attend color to identify targets. An asymmetric N170 ERP component (larger amplitude over left posterior hemisphere sites) was used as a marker of the early automatic processing of letter forms. Young and middle-aged subjects did not generate an asymmetric N170 component. In contrast, young-old and old-old subjects produced a larger N170 over the left hemisphere. Furthermore, older adults generated a larger N170 to letter than non-letter stimuli over the left, but not right hemisphere. More asymmetric N170 responses predicted greater allocation of late selection resources to target letters in the ignore color, as indexed by P3b amplitude. These results suggest that unlike their younger counterparts, older adults automatically process stimuli as letters early in the selection process, when it would be more efficient to attend to color only. The inability to ignore letters early in the processing stream helps explain the age-related increase in subsequent processing of target letter forms presented in the ignore color.
PMCID: PMC3907075  PMID: 24162742
aging; ERPs; N170; selective attention; P3b
3.  Sex differences in cocaine conditioned place preference in C57BL/6J mice 
Neuroreport  2014;25(2):105-109.
Men and women respond differently to the subjective effects of cocaine and cocaine-associated cues, which has implications for the development and maintenance of cocaine addiction. Preclinical studies performed in rats, modeling various aspects of cocaine addiction, have largely validated these results, indicating that female rats may be more sensitive to the rewarding properties of cocaine. The molecular mechanisms leading to sex differences in cocaine reward have largely not been determined, although sex hormones are thought to play a role. The mouse is commonly used as a model organism to study the molecular and genetic factors that influence a variety of psychiatric disorders. In particular, the inbred C57BL/6 mouse strain is often used for behavioral studies related to substance abuse. To begin to understand the hormonal, molecular and genetic mechanisms that might affect cocaine reward, we directly compared male and female C57BL/6J mice in cocaine conditioned place preference (CPP), a test that examines the rewarding and cue-associated properties of drugs of abuse. We conditioned mice at three doses of cocaine and examined preference and extinction of preference. We found that the acquisition of cocaine CPP did not differ between male and female mice. However, extinction of cocaine CPP was delayed in male mice compared to females at the lowest dose of cocaine. We conclude that sex differences in cocaine CPP can be observed in C57BL/6J mice at very low doses of cocaine.
PMCID: PMC4061045  PMID: 24145777
Conditioned place preference; cocaine; sex differences; C57BL/6; mice; reward
4.  Cocaine does not produce reward in absence of dopamine transporter inhibition 
Neuroreport  2009;20(1):9-12.
Previously we reported that knock-in mice with a cocaine-insensitive dopamine transporter (DAT-CI mice) do not experience cocaine reward, as measured by conditioned place-preference (CPP). This conclusion has come under scrutiny because some genetically modified mice show cocaine-induced CPP in a narrow dose range, i.e. responding at doses around 10 mg/kg, but not at 5 and 20 mg/kg, the doses we tested in DAT-CI mice. These results raise the possibility that we have missed the optimal dose for cocaine response. Here we report that cocaine does not produce reward in DAT-CI mice at low, moderate, and high doses, including 10 mg/kg. This study strengthens our conclusion that DAT inhibition is required for cocaine reward in mice with a functional dopaminergic system.
PMCID: PMC4277863  PMID: 18987557
Cocaine; dopamine transporter; knock-in mice; conditioned place preference
5.  Amygdala-Orbitofrontal Resting State Functional Connectivity is Associated with Trait Anger 
Neuroreport  2012;23(10):606-610.
An important distinction in research on the neural mechanisms of emotion regulation involves the relatively limited duration of emotional states vs. emotional traits which are defined as the stable tendency to experience particular emotions in daily life. Neuroimaging investigations of the regulation of anger states point to involvement of reciprocal changes in prefrontal cortex and amygdala activity, but the neural substrate of trait anger has received less attention. We used resting-state functional magnetic resonance imaging (rsfMRI) to determine whether variation in the strength of functional connectivity between amygdala and orbitofrontal cortex is associated with trait anger. Sixteen healthy male subjects completed the Speilberger State-Trait Anger Expression Inventory. Correlational analysis for resting-state functional connectivity (RSFC) was conducted with left and right amygdala as separate seed regions. Anger measures were correlated to RSFC involving right and left amygdala on a voxel-by-voxel basis across all subjects. We found that Trait Anger was inversely associated with the strength of RSFC between amygdala and contralateral middle orbitofrontal cortex. The association was stronger for the right amygdala-left orbitofrontal connection. Anger Control, the tendency to try to control expressions of anger, showed the opposite pattern of being positively correlated with amygdala-orbitofrontal connectivity. The present study provides evidence that RSFC in a cortico-limbic circuit might subserve stable differences in anger regulation. Our findings also suggest that RSFC may prove valuable as a trait marker for disorders characterized by emotional dysregulation such as depression, anxiety and personality disorders.
PMCID: PMC4271793  PMID: 22617448
functional magnetic resonance imaging; negative emotion; emotion regulation; prefrontal cortex
Neuroreport  2013;24(18):1067-1071.
With limited clinical trials in stem cell therapy for adult stroke underway, the assessment of efficacy also needs to be considered for neonatal hypoxic-ischemic brain injury, considering its distinct symptoms. The critical nature of this condition establishes deficits that last a lifetime. Here, we will highlight the progress of current translational research, commenting on the critical nature of the disease, stem cell sources, the use of hypothermia, safety and efficacy of each treatment, modes of action, and the possibility of combination therapy. With this in mind, we reference translational guidelines established by a consortium of research partners called Stem cell Therapeutics as an Emerging Paradigm for Stroke (STEPS). The guidelines of STEPS are directed for evaluating outcomes for cell therapy in adult stroke; however, we identify the overlapping pathology, as we believe these guidelines will serve well in the investigation of neonatal hypoxic-ischemic therapy. Lastly, discussion into current treatment and a case report demonstrate that the capabilities for these treatments have arrived and the time for advancing stem cell therapy and hypothermia for cerebral palsy is now.
PMCID: PMC3889715  PMID: 24169604
cell transplantation; neonatal hypoxic-ischemic injury; translational research; clinical applications
7.  Profiling metabolite changes in the neuronal differentiation of human striatal neural stem cells using 1H-Magnetic Resonance Spectroscopy 
Neuroreport  2013;24(18):1035-1040.
Neural stem cells (NSCs) are playing an increasing clinical role for stroke. However at present, it is not yet possible to non-invasively monitor their differentiation once implanted into the brain.
We here describe the use of high-resolution 1H-magnetic resonance spectroscopy (MRS) to define a metabolite profile of undifferentiated human striatal NSCs from the STROC05 cell line and their differentiation after 3 weeks of treatment with purmorphamine.
The undifferentiated conditions were characterized by ∼95% of cells expressing nestin and ∼77% being Ki67+, indicating that these were still proliferating. Phosphophocholine+glycerophosphocholine (PC+GPC) was increased in these cells, as well as myo-Inositol (mI). PC+GPC and mI were dramatically reduced upon differentiation, potentially serving as markers of the NSC state. Upon differentiation (∼45% neurons, ∼30% astrocytes, ∼13% oligodendrocytes), the concentration of many metabolites decreased in absolute value. The decreasing trend of the N-acetyl-aspartate (NAA) level was observed in differentiated cells when compared to NSCs. An increase in plasmalogen (enriched in myelin sheets) could potentially serve as a marker of oligodendrocytes.
These metabolite characteristics of undifferentiated and differentiated NSCs provide a basis for exploring their possible use as markers of differentiation after cell transplantation.
PMCID: PMC3991110  PMID: 24145773
Neural Stem Cell; 1H-Magnetic Resonance Spectroscopy; Purmorphamine; DARPP-32; Neuronal Differentiation; Metabolites; Striatum; Ganglionic Eminence; human
8.  Variation in the topography of the speech production cortex verified by cortical stimulation and high gamma activity 
Neuroreport  2014;25(18):1411-1417.
Supplemental Digital Content is available in the text.
In this study, we have addressed the question of functional brain reorganization for language in the presence and absence of anatomical lesions in two patients with epilepsy using cortical stimulation mapping and high gamma (HG) activity in subdural grid recordings. In both, the expressive language cortex was defined as the cortical patch below the electrode(s) that when stimulated resulted in speech arrest, and during speech expression tasks generated HG activity. This patch fell within the borders of Broca’s area, as defined anatomically, in the case of the patient with a lesion, but outside that area in the other, lesion-free patient. Such results highlight the necessity for presurgical language mapping in all cases of surgery involving the language-dominant hemisphere and suggest that HG activity during expressive language tasks can be informative and helpful in conjunction with cortical stimulation mapping for expressive language mapping.
PMCID: PMC4232293  PMID: 25371284
Broca’s area; cortical stimulation mapping; high gamma activity; presurgical language mapping; speech production area
9.  Effects of exercise on resting-state default mode and salience network activity in overweight/obese adults 
Neuroreport  2013;24(15):866-871.
Despite the common use of exercise as a weight loss strategy, little is known about its neuronal effects, and how these may be related to cognitive changes that impact food intake. The current study assessed the effects of a 6-month exercise intervention on intrinsic activity in the default mode network (DMN), a functionally connected network of brain regions including posterior cingulate cortex, cuneus/precuneus, medial prefrontal cortex, medial temporal lobe, and inferior parietal cortices, and salience network, which includes the anterior cingulate cortex and insula. Resting-state functional magnetic resonance imaging (fMRI) data were acquired in 12 overweight/obese individuals. The intervention was associated with a reduction in DMN activity in the precuneus (p=0.003, FWE-corrected), which was associated with greater fat mass loss (p=0.013) as well as reduced perceived hunger (Three Factor Eating Questionnaire, p=0.024) and hunger ratings in response to a meal (p=0.013). No changes were observed in the salience network in response to the exercise intervention. The association between DMN change and both fat mass loss and reduction of hunger ratings suggests that DMN function may be involved in the regulation of food intake behaviors. Given previous reports of DMN overactivity in overweight/obese individuals, the present findings may indicate an exercise-related “normalization” of network function.
PMCID: PMC3937986  PMID: 24022176
exercise; obesity; default network; salience network; fMRI
10.  Progesterone withdrawal increases the anxiolytic actions of gaboxadol: role of α4βδ GABAA receptors 
Neuroreport  2003;14(1):43-46.
Hippocampal α4βδ GABAA receptors (GABAA-R) are increased following progesterone withdrawal (PWD) in a rodent model of premenstrual anxiety. This α4βδ receptor isoform uniquely responds to the GABA agonist gaboxadol (THIP) with a maximum current greater than that gated by GABA, and is potentiated more by pentobarbital than are other GABAA-R. We therefore investigated the anxiolytic effects of these drugs using the elevated plus maze. Gaboxadol (1.25 mg/kg) was markedly more anxiolytic in animals undergoing PWD than in controls. Pentobarbital (10 mg/kg) also produced a greater anxiolytic effect during PWD. These results suggest that the pharmacological properties of α4βδ GABAA-R following PWD are evident behaviorally. Alterations in the α4βδ GABAA-R population may have implications for the etiology and treatment of premenstrual syndrome.
PMCID: PMC4167748  PMID: 12544828
α4 subunit; Allopregnanolone; Anxiety; Extra-synaptic; δ subunit; GABAA receptor; Neurosteroid; Premenstrual syndrome; Progesterone; Tonic current
11.  Do TRPC channels mediate cholinergic excitation of cortical pyramidal neurons? 
Neuroreport  2013;24(10):550-554.
Activation of M1-type muscarinic acetylcholine receptors excites neocortical pyramidal neurons, in part by gating a non-selective cation conductance that produces calcium-dependent “afterdepolarizing potentials” (ADPs) following short trains of action potentials. While the identity of the cation conductance mediating the ADP is not known, previous work has implicated canonical transient potential receptor (TRPC) channels, specifically of the TRPC5 and TRPC6 subtypes. Using pharmacological and genetic approaches, we tested the role of TRPC channels in generating cholinergic ADPs in layer 5 pyramidal neurons in the mouse medial prefrontal cortex (mPFC). A variety of compounds that block TRPC channels, including 2-aminoethoxydiphenyl borate (2-APB), flufenamic acid, lanthanum, SKF-96365, and Pyr-3, had little, if any, impact on cholinergic ADPs. Similarly, genetic deletion of several TRPC subunits, including TPRC1, TRPC5, and TRPC6 (single knockouts), or both TRPC5 and TRPC6 together (double knockout), failed to reduce the amplitude of cholinergic ADPs. These data suggest that TRPC5 and TRPC6 subunits are not required for cholinergic excitation of layer 5 pyramidal neurons in the mouse mPFC, and suggest that the focus of future work should be expanded to test the involvement of other potential ionic effectors.
PMCID: PMC4151306  PMID: 23652155
Neocortex; Pyramidal Neuron; Acetylcholine; Afterdepolarization; TRPC channel; TRPC5 channel; TRPC6 channel; TRPC1 channel; Mouse; Muscarinic receptor
12.  N-linked glycosylation of cortical NMDA and kainate receptor subunits in schizophrenia 
Neuroreport  2013;24(12):688-691.
Dysfunctional glutamate neurotransmission has been implicated in the pathophysiology of schizophrenia. Abnormal expression in schizophrenia of ionotropic glutamate receptors (iGluRs) and the proteins that regulate their trafficking have been found to be region- and subunit-specific in brain, suggesting that abnormal trafficking of iGluRs may contribute to altered glutamatergic neurotransmission. The posttranslational modification N-glycosylation of iGluR subunits can be used as a proxy for their intracellular localization. Receptor complexes assemble in the lumen of the endoplasmic reticulum (ER), where N-glycosylation begins with the addition of N-linked oligomannose glycans, and subsequently is trimmed and replaced by more elaborate glycans while trafficking through the Golgi apparatus.
Previously, we found abnormalities in N-glycosylation of the GluR2 AMPA receptor subunit in schizophrenia. Here we investigated N-glycosylation of NMDA and kainate receptor subunits in dorsolateral prefrontal cortex from subjects with schizophrenia and a comparison group. We used enzymatic deglycosylation with two glycosidases: endoglycosidase H (Endo H), which removes immature high mannose containing sugars, and peptide-N-glycosidase F (PNGase F), which removes all N-linked sugars. The NR1, NR2A, NR2B, GluR6 and KA2 subunits were all sensitive to treatment with Endo H and PNGase F. The GluR6 kainate receptor subunit was significantly more sensitive to Endo H-mediated deglycosylation in schizophrenia, suggesting a larger molecular mass of N-linked high mannose and/or hybrid sugars on GluR6. This finding, taken with our previous work, suggests that a cellular mechanism underlying abnormal glutamate neurotransmission in schizophrenia may involve abnormal trafficking of both AMPA and kainate receptors.
PMCID: PMC3919653  PMID: 23820740
schizophrenia; postmortem brain; psychosis; kainate; glutamate receptors; prefrontal cortex
13.  Between Site Reliability of Startle Prepulse Inhibition Across Two Early Psychosis Consortia 
Neuroreport  2013;24(11):626-630.
Prepulse inhibition (PPI) and reactivity of the acoustic startle response are widely used biobehavioral markers in psychopathology research. Previous studies have demonstrated that PPI and startle reactivity exhibit substantial within-site stability; between-site stability, however, has not been established. In two separate consortia investigating biomarkers of early psychosis, traveling subjects studies were performed as part of quality assurance procedures in order to assess the fidelity of data across sites. In the North American Prodromal Longitudinal Studies (NAPLS) Consortium, 8 normal subjects traveled to each of the 8 NAPLS sites and were tested twice at each site on the startle PPI paradigm. In preparation for a binational study, 10 healthy subjects were assessed twice in both San Diego and Mexico City. Intraclass correlations between and within sites were significant for PPI and startle response parameters, confirming the reliability of startle measures across sites in both consortia. There were between site differences in startle magnitude in the NAPLS study that did not appear to be related to methods or equipment. In planning multi-site studies, it is essential to institute quality assurance procedures early and establish between site reliability to assure comparable data across sites.
PMCID: PMC4135529  PMID: 23799460
Endophenotype; Reliability; Startle; Prepulse Inhibition
14.  Electrophysiological and Hemodynamic Responses to Reward Prediction Violation 
Neuroreport  2009;20(13):1140-1143.
Anterior cingulate cortex has been functionally linked to the detection of outcomes that are worse than expected using both scalp electrophysiological (ERP) and hemodynamic (fMRI) responses. The current study used a reward prediction violation design acquired both ERP and fMRI data from the same participants in different sessions. Both the medial frontal negativity (MFN) ERP response and anterior cingulate cortex hemodynamic activity differentiated between reward delivery and expectation with the largest MFN and anterior cingulate cortex response when predicted rewards were not delivered. Inverse modeling placed the MFN source near the anterior cingulate cortex hemodynamic activation. The fMRI study also showed increased striatal response to rewards regardless of prediction indicating dissociation of neural processing of reward and reward expectation.
PMCID: PMC4095766  PMID: 19690501
Reward; Event Related Potentials; fMRI; anterior cingulate cortex
15.  Greater neuronal responses during automatic semantic processing in schizophrenia 
Neuroreport  2013;24(5):212-216.
A core feature of schizophrenia is a disturbance of associative processes. To date, no functional MRI studies have investigated semantic priming in schizophrenia under experimental conditions that measure automatic, as opposed to strategic, processing. The present study’s focus was to investigate hemodynamic responses during indirect semantic priming at a short stimulus onset asynchrony (i.e. 350 ms), conditions which are considered to be a particularly sensitive measure of automatic spreading activation during semantic processing and of the associative disturbances in schizophrenia. Seventeen individuals with DSM-IV, schizophrenia and 15 comparison participants underwent functional scanning while performing a lexical decision task on directly related, indirectly related, unrelated, and word/nonword pairs. A random-effects region of interest analysis within a priori temporal and frontal regions was performed. Whereas comparison individuals exhibited hemodynamic suppression in response to priming, individuals with schizophrenia exhibited hemodynamic enhancement. Relative to the comparison group, these enhancements were observed in the left fusiform and superior temporal gyri for indirectly related word pairs relative to unrelated pairs. Greater priming-related responses within temporal regions may reflect increased and prolonged automatic spreading activation during semantic processing in schizophrenia.
PMCID: PMC4086909  PMID: 23399997
functional magnetic resonance imaging; fusiform gyrus; schizophrenia; semantic priming; superior temporal gyrus
16.  Regulation of TREM2 expression by an NF-κB-sensitive miRNA-34a 
Neuroreport  2013;24(6):318-323.
Genetic deficits and loss of function for the triggering receptor expressed in myeloid cells 2 (TREM2; encoded at chr6p21.1), a transmembrane spanning stimulatory receptor of the immunoglobulin/lectin-like gene superfamily, have been associated with deficiencies in phagocytosis and the innate immune system in Alzheimer’s disease. In this study, we provide evidence that TREM2 is downregulated in samples of sporadic Alzheimer hippocampal CA1 compared with age-matched controls. A nuclear factor-κB (NF-κB)-sensitive miRNA-34a (encoded at chr1p36.22), upregulated in Alzheimer’s disease, was found to target the 299 nucleotide human TREM2 mRNA 3′-untranslated region (3′-UTR) and downregulate the expression of a TREM2-3′-UTR reporter vector. A stabilized anti-miRNA-34a (AM-34a) quenched this pathogenic response. The results suggest that an epigenetic mechanism involving an NF-κB-mediated, miRNA-34a-regulated downregulation of TREM2 expression may shape innate immune and phagocytic responses that contribute to inflammatory neurodegeneration.
PMCID: PMC4072209  PMID: 23462268
Alzheimer’s disease; amyloidosis; hippocampal CA1; innate immune response; microglial cells; miRNA-34a; NF-κB; phagocytosis; TREM2
17.  Magnetoencephalographic evidence for a precise forward model in speech production 
Neuroreport  2006;17(13):1375-1379.
Electroencephalography and magnetoencephalography studies have shown that auditory cortical responses to self-produced speech are attenuated when compared with responses to tape-recorded speech, but that this attenuation disappears if auditory feedback is altered. These results suggest that auditory feedback during speaking is processed by comparing the feedback with its internal prediction. The present study used magnetoencephalography to investigate the precision of this matching process. Auditory responses to speech feedback were recorded under altered feedback conditions. During speech production, the M100 amplitude was maximally reduced to the participants' own unaltered voice feedback, relative to pitch-shifted and alien speech feed back. This suggests that the feedback comparison process may be very precise, allowing the auditory system to distinguish between internal and external sources of auditory information.
PMCID: PMC4060597  PMID: 16932142
altered feedback; efference copy; magnetoencephalography; speech production
18.  Brain Potentials and Repetition Effects During Encoding and Retrieval of Words 
Neuroreport  2008;19(14):1365-1368.
Using Event-Related Potentials (ERPs), the present study utilized a study-test paradigm to investigate the existence of a common mechanism underlying repeated learning effects during encoding and retrieval. Results showed repeated learning effects occurred in both encoding and retrieval. However, the effect of encoding appeared earlier and lasted longer than that of retrieval. Furthermore, the effect of implicit retrieval appeared earlier than that of explicit retrieval. The main scalp distributions of the repetition effects related to both encoding and retrieval occurred at parietal and central sites. Both ERP repetition effects manifested significantly larger and positive-going ERP response of repeated words compared to the words’ first appearance. The ERP repetition effects support the hypothesis that there is common learning-related automatic processing during encoding and retrieval.
PMCID: PMC4058855  PMID: 18766012
encoding; retrieval; implicit memory test; explicit memory test; repetition enhancement
19.  Age differences in thalamic low frequency fluctuations 
Neuroreport  2013;24(7):349-353.
The thalamus plays a role in many different types of cognitive processes and is critical for communication between disparate cortical regions. Given its critical role in coordinating cognitive processes, it is important to understand how its function might be affected by aging. In the present study, we examined whether there are age differences in low-frequency fluctuations during rest in the thalamus. Across independent datasets, we found that the amplitude of low frequency (.01–.10 Hz) oscillations was greater in the thalamus among older than younger adults. Breaking this low frequency range down further revealed that this increase in amplitude with age in the thalamus was most pronounced at the low end of the frequency range (.010–.027 Hz), whereas in the higher low frequency range (.198–.250 Hz) younger adults showed greater amplitude than older adults. These shifts in thalamic low frequency oscillatory activity likely influence the complex dynamics of coordinated brain activity and influence cognitive performance.
PMCID: PMC4048729  PMID: 23571657
aging; thalamic oscillatory activity; fALFF
20.  Increased oxygen load in the prefrontal cortex from mouth breathing: a vector-based near-infrared spectroscopy study 
Neuroreport  2013;24(17):935-940.
Individuals who habitually breathe through the mouth are more likely than nasal breathers to have sleep disorders and attention deficit hyperactive disorder. We hypothesized that brain hemodynamic responses in the prefrontal cortex might be different for mouth and nasal breathing. To test this hypothesis, we measured changes in oxyhemoglobin and deoxyhemoglobin in the prefrontal cortex during mouth breathing and nasal breathing in healthy adults (n=9) using vector-based near-infrared spectroscopy. The angle k, calculated from changes in oxyhemoglobin and deoxyhemoglobin and indicating the degree of oxygen exchange, was significantly higher during mouth breathing (P<0.05), indicating an increased oxygen load. Mouth breathing also caused a significant increase in deoxyhemoglobin, but oxyhemoglobin did not increase. This difference in oxygen load in the brain arising from different breathing routes can be evaluated quantitatively using vector-based near-infrared spectroscopy. Phase responses could help to provide an earlier and more reliable diagnosis of a patient’s habitual breathing route than a patient interview.
PMCID: PMC4047298  PMID: 24169579
hemodynamic response; mouth breathing; nasal breathing; oxygen load; vector-based near-infrared spectroscopy
21.  The effect of the sympathetic nervous system on splenic natural killer cell activity in mice administered the Lactobacillus pentosus strain S-PT84 
Neuroreport  2013;24(17):988-991.
Splenic sympathetic nerve activity (SNA) modulates cellular immune functions such as splenic natural killer cell activity. Lactobacillus pentosus strain S-PT84 enhances splenic natural killer cell activity. Here, we examined whether S-PT84 affects splenic natural killer activity through splenic SNA in BALB/c mice. Splenic SNA was significantly decreased following the administration of S-PT84. This phenomenon was inhibited by pretreatment with thioperamide (histamine H3 receptor antagonist), suggesting that S-PT84 directly affected splenic SNA. Thioperamide also inhibited the increase in splenic natural killer activity by S-PT84. Thus, the change in splenic natural killer activity by S-PT84 may be partially modulated through SNA.
PMCID: PMC4047316  PMID: 24165047
Lactobacillus pentosus strain S-PT84; splenic natural killer cell activity; splenic sympathetic nerve activity; thioperamide
22.  Gamma phase-locking modulated by phonological contrast during auditory comprehension in reading disability 
Neuroreport  2012;23(14):851-856.
Children with specific reading impairment may have subtle deficits in speech perception related to difficulties in phonological processing. The aim of this study was to examine brain oscillatory activity related to phonological processing in the context of auditory sentence comprehension using magnetoencephalography (MEG) to better understand these deficits. Good and poor readers, 16-18 years of age, were tested on speech perception of sentence-terminal incongruent words that were phonologically manipulated to be similar or dissimilar to corresponding congruent target words. Functional coupling between regions was measured using phase-locking values (PLV). Gamma band (30-45 Hz) PLV between auditory cortex and superior temporal sulcus in the right hemisphere was differentially modulated in the two groups by the degree of phonological contrast between the congruent and incongruent target words in the latency range associated with semantic processing. Specifically, the PLV was larger in the phonologically similar than in the phonologically dissimilar condition in the good readers. This pattern was reversed in the poor readers, whose lower PLV in the phonologically similar condition may be indicative of the group's impaired phonological coding abilities, and consequent vulnerability under perceptually demanding conditions. Overall, the results support the role of gamma oscillations in spoken language processing.
PMCID: PMC4043393  PMID: 22889887
speech perception; phonological processing; sentence context; phase-locking value; gamma band oscillations; magnetoencephalography
23.  Prazosin differentially affects extinction of cocaine CPP based on dose and initial preference 
Neuroreport  2012;23(18):1048-1051.
Recent work has demonstrated that α1-adrenergic receptor blockade impairs extinction in fear conditioning paradigms in rodents. However, studies of the role of α1-adrenergic receptors in extinction using other conditioning paradigms, such as those examining the conditioned effects of drug of abuse, have provided inconsistent results. In this article, we reanalyze and extend previously-reported findings of the effect of prazosin, an α1-adrenergic receptor antagonist, on the extinction of a cocaine-induced condition place preference in rats, using a median split of performance during the initial test for preference. This new reanalysis, which includes further extinction testing, revealed a paradoxical dose effect. A single post-test administration of a lower dose of prazosin, 0.3 mg/kg IP, impaired extinction in rats that demonstrated a below-median preference during initial testing, but had no effect on extinction in rats that demonstrated an above-median preference during initial testing. In contrast, a single post-test administration of a higher dose of prazosin, 1.0 mg/kg IP, enhanced extinction in rats that demonstrated an above-median preference during initial testing, but had no effect on extinction in rats that demonstrated a below-median preference during initial testing. Consistent with other studies of fear and drug conditioning, these results suggest the involvement of the α1-adrenergic receptor in the formation of extinction memories, but also indicate a potentially important differential effect on extinction based on the dose of prazosin and the strength of the initial learning.
PMCID: PMC3984259  PMID: 23108042
extinction; drug conditioning; cocaine; conditioned place preference; memory; reconsolidation
24.  Detection of silent gaps in white noise following cortical deactivation in rats 
Neuroreport  2008;19(8):893-898.
Rodent studies employing cortical removal techniques, ranging from transient deactivation to surgical ablation of cortex, reveal the importance of auditory cortical integrity in detecting short silent gaps in white noise (2–15 ms; [1,2]). Processing limits for longer gaps under decorticate conditions in rats remain unknown. Determining the temporal threshold for sub-cortical resolution of gaps in noise could, however, shed light on both normal hierarchical processing of acoustic temporal stimuli, as well as the etiology of processing anomalies following developmental cortical disruption [3,4,5,6,7,8]. To address these important issues, we assessed whether intact rats, as well as those with induced developmental cortical disruptions (microgyria), could resolve silent gaps of 20 to 100 ms in duration when embedded in white noise, during functional deactivation of auditory cortex. Results showed that both intact rats, as well as those with cortical malformations resulting from early focal disruptions of neuronal migration, could resolve silent gaps of 100 ms duration under cortical deactivation (KCl). However, only intact rats could reliably detect 75 ms gaps, suggesting possible sub-cortical anomalies in subjects with early cortical disturbances.
PMCID: PMC3955703  PMID: 18463508
Auditory temporal processing; Sub-cortical; Startle response; Developmental injury; Learning impairment
25.  Functional recruitment of visual cortex for sound encoded object identification in the blind 
Neuroreport  2009;20(2):132-138.
Individuals using a visual-to-auditory sensory substitution device (SSD) called ‘The vOICe’ can identify objects in their environment through images encoded by sound. We have shown that identifying objects with this SSD is associated with activation of occipital visual areas. Here, we show that repetitive transcranial magnetic stimulation (rTMS) delivered to a specific area of occipital cortex (identified by functional MRI) profoundly impairs a blind user’s ability to identify objects. rTMS delivered to the same site had no effect on a visual imagery task. The task and site-specific disruptive effect of rTMS in this individual suggests that the cross-modal recruitment of occipital visual areas is functional in nature and critical to the patient’s ability to process and decode the image sounds using this SSD.
PMCID: PMC3951767  PMID: 19104453
blindness; occipital cortex; plasticity; repetitive transcranial magnetic stimulation; sensory substitution

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