9-11 Despite decades of effort to validate these hypotheses, documentation of abnormalities of DA function in schizophrenia has remained elusive. Postmortem studies measuring DA and its metabolites and receptors in the brains of schizophrenic patients have yielded inconsistent, or inconclusive results

(for a review, see reference 11). The lack of clear evidence for altered dopaminergic indices in schizophrenia might, indicate that DA transmission is abnormal only relative to Inhibitors,research,lifescience,medical other systems, such as the glutamatergic system.12 On the other hand, the absence of data supporting the DA hypothesis of schizophrenia might be due to the difficulty in obtaining a direct measurement of DA transmission in the living human brain. However, over

the last, few years, progress in brain-imaging methods has enabled direct, measurement of DA transmission at the D2 receptor, and the application of these techniques to the study of schizophrenia has provided new insights into the nature and the Inhibitors,research,lifescience,medical role of DA function dysregulation in schizophrenia. This paper will briefly review these data, and explore the implications of these results in terms of pathophysiology and treatment. Brain imaging as a tool for measuring DA synaptic activities Neuroreceptor imaging with positron emission tomography (PET) and single-photon emission computed tomography (SPECT) are classically Inhibitors,research,lifescience,medical aimed at measuring neuroreceptor parameters in the living human brain. More recently, several groups have demonstrated that under specific conditions, in vivo neuroreceptor Inhibitors,research,lifescience,medical binding techniques can also be used to measure acute fluctuations in the concentration of the endogenous transmitters in the vicinity of radiolabeled

receptors.13-16 Competition between radiotracers and transmitters for binding to neuroreceptors is the principle underlying this technique, though other mechanisms such as agonist-induced receptor internalization might also play a role (for a review, see Inhibitors,research,lifescience,medical reference 17). So far, applications of this new paradigm have been developed mainly to study DA transmission at D2 receptors. Endogenous competition between DA and radiolabeled D2 receptor ligands found was initially documented in ex vivo studies performed in rodents. Amphetamine, which releases DA and thereby increases endogenous DA synaptic concentration,18,19 reduced the in vivo binding of the D2 agonist [3H]-N-propylnorapomorphine20,21 and the D2 antagonist [3H]raclopride.22,23 Reduced in vivo accumulation of D2 tracers was also reported KPT-330 clinical trial following pretreatment with the DA uptake inhibitors amfonelic acid and methylphenidate.21 The opposite effect, (ie, increased tracer accumulation) was induced by drugs that decrease DA endogenous concentration, such as reserpine and γ-butyrolactone.21,23-26 These interactions suggested that PET and SPECT could be used to measure acute fluctuations in endogenous DA.

One method to assess noradrenergic function in PTSD has been to measure plasma NF, levels or levels of NE metabolites in 24-hour urine collections. Studies have found increased urinary concentrations of NE among hospitalized PTSD patients compared with hospitalized patients

with other mental disorders.9 Similar findings have been reported in sexually abused children compared with healthy controls.10 Other investigators have noted decreases in the density of platelet cell α2-adrenergic receptors in combat veterans with PTSD and in traumatized children.11,12 Reduction of these NE-binding receptors may indicate an adaptive downregulation in response to chronically elevated plasma NE levels. Since the noradrenergic Inhibitors,research,lifescience,medical axil also modulates peripheral autonomic

responses, investigators have also assessed noradrenergic function in Inhibitors,research,lifescience,medical PTSD by comparing autonomic sesponses in PTSD subjects and controls. Automnomic measures in these studies have includes heart rate, systolic and diastolic blood pressure, and galvanic skin responses. While early studyies13,14 noted baseline autonomic differences between combat veterans with PTSD and non-PTSD controls, later studies15-17 did not control Inhibitors,research,lifescience,medical for the effects of anticipatory anxiety and study demand characteristics.18,19 Studies that have compared autonomic responses in PTSD and non-PTSD subjects to stressful but nontraumatic stimuli such as having to perform arithmetic caclulations20,21 or watch unpleasant Inhibitors,research,lifescience,medical films16,22 have not identified autonomic differences between PTSD subjects and controls. Thus, there is little evidence to suggest that PTSD

involves changes in resting autonomic function or in autonomic responsivity to nontraumatic stimuli. In contrast to these negative findings, there is compelling evidence to indicate that individuals with PTSD exhibit an increased autonomic responsivity to trauma-related stimuli. Compared with traumaexposed controls, PTSD subjects exhibit greater autonomic arousal to trauma-related stimuli such as audiotapes of combat sounds,13,14,23 videotapes of war zone scenes,16,24 and trauma-related smells.25 Inhibitors,research,lifescience,medical Pitman et al22 noted increased autonomic arousal in PTSD subjects using a script-driven imagery technique in which trauma survivors listened to their own trauma narrative while viewing trauma-related slides. These findings prompted a multisite Veterans Affairs Cooperative Study to evaluate Calpain the diagnostic utility of psychophysiological assessments in Vietnam combat veterans with PTSD.21 This study included three groups: veterans with current PTSD (n=778), veterans with lifetime but not current PTSD (n=181), and veterans who never had PTSD (n=369). Using physiological variables alone, researchers correctly TSA HDAC price classified 67 % of the current PTSD group and a similar percentage of the non-PTSD group. Collectively, these studies suggest that increased autonomic reactivity to traumatic stimuli is an important feature of manyindividuals with PTSD.

Authors’ contributions HHB was involved in the study conception and design, data collection, analysis, revision, editing and manuscript writing. MH participated to the study conception and design, writing-up and DAPT research buy finalization of the manuscript. HK was involved in the conception and design of study and took an active part in the data analysis and results interpretation. DKZ contributed to the data collection and helped to analyze and interpret the data and to write the manuscript. EJ participated to the Inhibitors,research,lifescience,medical study design, analysis and results

interpretation and writing-up of the manuscript. All authors read and approved the final Inhibitors,research,lifescience,medical manuscript. Pre-publication history The pre-publication history for this paper can be accessed here: http://www.biomedcentral.com/1471-227X/10/20/prepub Acknowledgements This study was sponsored by the Iranian Ministry of Health and Medical Education. The authors wish to thank all participants for their support and involvement in this study. We also, thank Dr Ahmadreza Djalali for his useful comments.
Acute appendicitis is one of the most common reasons for acute abdomen [1]. Diagnosis based

on clinical evaluation only is difficult and results in high negative appendectomy rates and missed Inhibitors,research,lifescience,medical diagnoses [2,3]. Negative appendectomies increase mortality, prolong hospital stay, and increase the risk of infectious complications [4]. Appendicitis is missed in approximately 12% of patients, Inhibitors,research,lifescience,medical increasing the risk of perforated appendicitis, peritonitis, abscesses and leading Inhibitors,research,lifescience,medical to a two to tenfold increased

mortality rate [5-7]. The use of ultrasonography (US) and computed tomography (CT) to support clinical diagnosis is widespread [8]. US has considerable accuracy limitations, as it generates too many false negative results. Although CT is more accurate, it fails in 12% of patients and results in considerable ionizing radiation exposure in often young individuals. This ionizing radiation exposure Tryptophan synthase is associated with the risk of cancer induction and cancer related death [9]. Iodinated contrast medium administration may also induce nephropathy or aggravate existing nephropathy. MRI is a potential replacement for CT, without associated ionizing radiation and contrast medium administration. If proven to be sufficiently accurate, MRI could be introduced in the diagnostic pathway of patients with suspected appendicitis, increasing diagnostic accuracy and improving clinical outcome, without the risk of radiation induced cancer or iodinated contrast medium-related drawbacks.

In 1978 Vaughan et al. described their preclinical and clinical experiences with the CO2 laser in the setting of laryngeal tumors.3,4 Primarily, the CO2 laser could be utilized either to debulk tumors, restore airway patency, or to treat smaller tumors with an oncologically sound resection. Patients were generally reported

to suffer little morbidity, allowing for short hospitalizations Inhibitors,research,lifescience,medical and adequate function with regard to swallowing and voice. Importantly, the authors described the ability to avoid a tracheostomy, which is associated with substantial morbidity and cost. Davis et al. and Lacourreye et al. also described utilization of the CO2 laser for the purpose of debulking in the 1980s.5,6 Specifically, they suggested that partial endoscopic excision of obstructing lesions (using single or Palbociclib cell line repeated treatments) can be an alternative to emergency tracheotomy or emergency laryngectomy whenever airway control can be initially ensured by endotracheal intubation. Since Inhibitors,research,lifescience,medical the 1970s, utilization of TLM has become an important tool in the management of laryngeal tumors,

and in certain centers it is considered one of the primary definitive treatment modalities for early-stage disease. TECHNIQUE/LIMITATIONS Although initially designed to be used Inhibitors,research,lifescience,medical in the treatment of early laryngeal tumors in the 1970s, by the 1990s, TLM was being utilized for all tumor categories, primarily through the efforts

of Steiner and colleagues.7–9 A detailed technical description of TLM is beyond the scope of this review. Authors have described Inhibitors,research,lifescience,medical a wide variety of procedures using the CO2 laser system, ranging from partial supraglottectomies (removal of a portion or the entire epiglottis, arytenoids, ary-epiglottic folds) to partial glottectomies to near-total laryngectomy.10 Inhibitors,research,lifescience,medical A detailed description of cordectomy procedures was provided in 2000 by the European Laryngology Society; these range from type I subepithelial cordectomy to type V which represent extended cordectomies encompassing either supraglottic or subglottic structures.11,12 Irrespective of the extent of surgery, TLM is based upon a number of fundamental principles that diverge substantially from traditional oncological approaches (Figure 1). First, in contrast to traditional surgical resection with en bloc tumor removal, with TLM, large tumors Dichloromethane dehalogenase can be removed in a piecemeal fashion, usually as two specimens. The final tumor is then reassembled ex vivo for pathologic analysis of margins. Often, the epiglottis is bisected in the sagittal plane, with each hemi-larynx removed separately. In addition, since all margins are obtained using a CO2 laser, a pathologist trained in evaluating tissue removed via laser resection is required. As was demonstrated by Mannelli et al.

As examples, nonsteroidal antiinflammatory drugs and histamine receptor antagonists are both widely used in their prescription and over-the-counter forms. Both are occasionally mentioned as causes of confusion. For some medications, conflicting data exist regarding whether the medication itself can be independently implicated in causing cognitive impairment, (eg, histamine receptor antagonists)64 or whether the elderly are more sensitive to a particular undesirable effect, (eg, alprazolam).65 Some medications may indirectly participate in causing cognitive difficulties by impairing normal excretion of a drug with CNS effects.66 Such drug

interactions Inhibitors,research,lifescience,medical arc most common with the very potent inhibitors of drug metabolism (eg, ketoconazole inhibition of CYP3 A4).67 The same may prove to be true of inhibition of drug transport. For www.selleckchem.com/autophagy.html herbal and other dietary Inhibitors,research,lifescience,medical supplements, there are few data available to make any kind of assessment. In spite of assigned “likelihood” for causing undesirable CNS effects, any change in cognitive function that occurs during the course of any drug or “health aid” therapy should immediately prompt the consideration

that medication or supplements may be involved. This is particularly Inhibitors,research,lifescience,medical true for the frail elderly and those hospitalized in critical care settings. Medications with anticholinergic characteristics These medications can cause a wide range of symptomatology ranging from deficits in attention and memory to florid delirium. Anticholinergic activity can be found in drugs across many therapeutic classes. Scopolamine is used to model the memory deficits found in Alzheimer’s disease.68 Atropine and scopolamine can cause delirium even in low doses and when used as mydriatics.22 Inhibitors,research,lifescience,medical Oxybutynin, cyclobenzaprine, diphenhydramine, trihexyphenidyl, benztropine, doxepin, amitriptyline, clomipramine, trimipraminc, imipramine, protriptylinc, clozapine, chlorpromazine, chlorprothixene, and Inhibitors,research,lifescience,medical thiothixene are just some of the drugs that possess significant anticholinergic activity.63

Psychotropic characteristics of some of the above, such as the tricyclic antidepressants and neuroleptics, may be additive with the anticholinergic properties PDK4 in causing undesirable symptomatology. It should be noted that proper drug treatment, of geriatric depression has been shown to improve cognitive abilities even when accompanied by slight increases in serum anticholinergicity.69 Sedative-hypnotics A variety of effects are detectable and vary with the use pattern and particular drug. Some “toxicity” can be viewed as an extension of therapeutic effect. The benzodiazepines have received extensive study.28,37,38 Following acute and chronic benzodiazepine administration, aged individuals may achieve higher plasma levels, with consequently more pronounced sedation and performance impairment. In addition, the aged may exhibit increased sensitivity to some benzodiazepines.

Figure 1 A. Negative for dysplasia – There is columnar cell metaplasia including mucin-filled, blue-tinted goblet cells. The glands are well spaced with abundant intervening lamina propria and the nuclei are regular, smooth, and basally aligned [hematoxylin and … Indefinite for dysplasia – This category is applied to biopsies where the changes seen cannot be definitively Inhibitors,research,lifescience,medical described as reactive or neoplastic. It is most often used in the presence of pronounced inflammation or the loss of surface epithelium. Cytologicatypia

characterized by hyperchromasia, overlapping nuclei, irregular nuclear borders, and nuclear stratification can be seen in the deep glands or the sides of villiform structures while the surface epithelium is free of atypia. The architecture should be largely normal with, at the Inhibitors,research,lifescience,medical most, minimal gland crowding. Surface maturation is present (Figure 1B). Low grade dysplasia – The most important feature of low grade dysplasia is cytologicatypia extending to the mucosal surface and either minimal

or absent surface maturation. Severe architectural distortion is not a feature, Inhibitors,research,lifescience,medical though mild gland crowding with decreased intervening lamina propria can be seen. Mitoses may be increased but no atypical forms should be seen. Inflammation is usually minimal. One important note: although cytologicatypia is a key finding, nuclear polarity is preserved. Loss of polarity – where the nucleus is tilted, rounded, or horizontal to the basement membrane – is associated with higher grade lesions (Figure 1C). High grade dysplasia – The cytologic changes are severe with markedly enlarged nuclei at the surface, pronounced pleomorphism, and at least focal Inhibitors,research,lifescience,medical loss of nuclear polarity. Surface maturation is lost. Mild to marked architectural distortion is a frequent finding, with crowded glands,

loss of lamina propria, focal budding, and/or cribriform glands. There should be no Etoposide concentration evidence of invasion into the lamina propria. Inhibitors,research,lifescience,medical Mitoses are increased and atypical mitoses may be seen. Ideally inflammation is almost minimal or absent. If either the cytologic or architectural changes are severe and extensive, the diagnosis of high grade dysplasia can be made even if other features are only low grade in severity (Figure 1D). Whenever high grade dysplasia is diagnosed the biopsy should also be evaluated for the presence of co-existing EAC. This may be difficult or impossible to exclude on biopsy, but suspicious or suggestive architectural changes include single cells in the lamina propria, desmoplasia, cribriform or solid tubular architecture, dilated tubules filled with necrotic debris, extensive neutrophilic infiltrate within the epithelium, ulcerated high grade dysplasia, and neoplastic tubules incorporated into the overlying squamous epithelium (57).

Their effects will be seen later, but not during the first few minutes of changes in enzyme activities. The use of canonical representations facilitates the initial model design. These representations, including uni- or multi-variate linear or power-law functions, permit the check details immediate translation of a dynamic interaction diagram into a symbolic, mathematical construct, which even at this early state allows certain diagnoses and analyses [21,22]. We demonstrate these strategies in the following section, starting with the main transcriptional regulators, MSN2 and MSN4. These are partially redundant, although MSN4, which Inhibitors,research,lifescience,medical is inducible by heat stress, is only mildly Inhibitors,research,lifescience,medical affected

by it [5]. 3.2. Canonical Modeling The development of a comprehensive mechanistic model of the transcriptional and translational processes is infeasible with our current modeling technologies, because the detailed physical and chemical events leading to the formation of an intact protein are exceedingly complex. Even within the realm of metabolism, which

is much better understood, the choice of a mechanistic model is not without problems. As a case in point, the Michaelis-Menten approximation is often chosen as a default model for enzyme catalyzed reactions, but this rate law is in truth somewhat problematic Inhibitors,research,lifescience,medical because its underlying assumptions are not satisfied in vivo [23,24]. For instance, the intracellular milieu is certainly not homogeneous and well mixed; the total amount of enzyme is likely Inhibitors,research,lifescience,medical to change as a function of time, and a substrate may not exist in much higher concentrations than its enzyme. Thus, one must question whether the Michaelis-Menten representation can be validly used to capture the dynamics of enzymatic processes

in vivo. Similarly, mass action kinetics is frequently used, but approximating the interactions between several Inhibitors,research,lifescience,medical proteins and RNAs in a crowded intracellular environment with an elementary reaction is probably not truly appropriate. At a very coarse level, the biological complexity and the need for relatively unbiased representations can be tamed to some degree by the use of canonical modeling representations, such as power-law functions, which time medroxyprogesterone and again have been shown to work well for the formalization of complex networks or systems. In particular, these functions are well suited as initial default representations for different types of interactions that are a priori ill characterized [25]. The use of power-law functions in such situations is a good compromise that does not impose linearity between components, is mathematically guaranteed to be correct at some nominal operating point, and often provides a reasonable approximation within an acceptable range of concentrations [26].

2005]. The weight gain with the use of such medications is considerably higher, as shown in a meta-analysis of over 80 studies on weight change during antipsychotic treatment, which showed a mean weight gain of 4.15 kg after 10 weeks of olanzapine use, 4.45 kg increase with clozapine use and 2.10 kg with risperidone compared with 1.08 kg with the typical antipsychotic haloperidol [Davis et al. 2003]. In our

study, the weight gain after 8 weeks of olanzapine use was almost twice as high (7.9 kg) as the value mentioned above. Also, the observed SWG among our patients Inhibitors,research,lifescience,medical (reaching 63.3% after 2 Selleckchem SCH772984 months and 67% of the patients after 12 months) was considerably higher compared with previously published data

concerning both Inhibitors,research,lifescience,medical short- and long-term use of olanzapine that point to a SWG (≥7%) affecting 15–50% of patients [Bobes et al. 2003; Jaton et al. 2003; Kinon et al. 2005]. This magnitude of weight change is not usual with patients already using other antipsychotics previously, but such a higher rate of weight gain has already been observed in a drug-naive young population (mean age Inhibitors,research,lifescience,medical 26.7 years), in which 77.1% presented with SWG after 1 year [Perez-Iglesias et al. 2008]. In that study the authors argued that the greater weight change was probably due to patients’ characteristics (drug-naive young people with a low prevalence of obesity, Inhibitors,research,lifescience,medical 4%) and to good treatment compliance (low dropout rates, good family support), reflecting regular use of the drug. Some of these characteristics were similar in our population; they

were also young (mean age 26.8 years), with a low prevalence of obesity (13.3%), and presented good treatment compliance because the initial treatment occurred while they were inpatients in our ward. Still, only 20% of our subjects were drug naive, which lead us to other possible reasons for the greater weight gain. One reasonable explanation for this could be the higher doses administered to our patients (mean 20.5 mg in the first month and 24 Inhibitors,research,lifescience,medical mg in the last measure after 12 months), which means that we surpassed the labeled maximum recommended dose. Although some of the literature data indicate a dose-dependent effect of olanzapine on weight gain [Simon et al. 2009], our population first was too homogeneous to make this analysis possible. Almost all participants ended up using similar high doses of olanzapine, with no significant dose-dependent effect being observed in our study. The majority of the subjects included in our study were already using another antipsychotic without good response (80%), with all of them being acutely ill and needing treatment as inpatients in our ward, which generally demands fast titration and higher end doses of antipsychotics, and therefore they are more likely to present with greater side effects.

Trypan blue staining was performed as the standard protocol. We used 0.4% Trypan blue to stain cells and counted the viable cells at each condition. All of the experiments were performed in duplicate for MTT assay. The MTT assays were performed as described by Gangzeng et al.14 Briefly, after electroporation in each condition, each 5×103 cells was seeded into a 96 well plate. After 24 h, Inhibitors,research,lifescience,medical 10% vol/vol of 5 mg/ml 3-(4, 5

dimethyl thiazol- 2-yl)-2, 5 diphenyl tetrazolium bromide (MTT, sigma, US) diluted in PBS was added into each well. The absorbance of this colored solution was quantified by ELLSA in 570 nm. Small Interfering RNA Transfection After electroporation and evaluation of the viability of the cells using MTT assay and Trypan blue staining, we chose the best electroporation condition (220 volt, exponential decay and 975 µF capacity). Then, siRNA transfection Inhibitors,research,lifescience,medical was performed in this condition. Small interfering RNA directed against DNMT1, and a non silencing siRNA were obtained from Eurofins MWG operon, Germany. The siRNA targeting DNMT1 Inhibitors,research,lifescience,medical was designed by Elbashir et al.15 The siRNA sense sequence was 5’-CGGUGCUCAUGCUUACAACTT-3’ and antisense sequence was 5’-GUUGUAAGCAU GAGCACCGTT-3’.

A non–silencing siRNA was used as a negative control. Its siRNA sequence was 5’-UUCUCCGAACGUGUCACGUdTdT-3’. Three concentrations of DNMT1 siRNA (10, 5 and 2 nmol) and non-silencing siRNA were each diluted in 50 µL DW, and was used for electroporation. Seventy two h after siRNA transfection cells were harvested to evaluate the DNMT1 protein. Western Blot Analysis The MDA-MB 468 cells treated with siRNA were used for total cell lysate preparation. The cells were washed with Inhibitors,research,lifescience,medical PBS solubilized in a lysis buffer www.selleckchem.com/products/Trichostatin-A.html containing Inhibitors,research,lifescience,medical 10 mM Tris-Hcl pH 7.4, 0.825 M NaCl and 1% ND-40, and then rotated in 4˚C for 15 min. Lysate was sonicated and cleared by centrifugation. Total protein was determined by Bradford method. Fifty µg of proteins of the transfected cells and control cells were mixed with lammali lysis buffer and resolved by 8% SDS-PAGE analysis. The gel

Oxymatrine was transferred onto nitrocellulose membrane following the standard protocol.16 The primary antibodies including anti-DNMT1 (Abcam, Canada) and anti-actin (Abcam, Canada) were used for immunoblotting. A horseredish peroxidase conjugated anti-mouse secondary Ab (Abcam, Canada) and chemiluminescenc substrate (ECL, Amersham Bioscience, UK) were used to determine the immuno labeled bands. All the experiments were performed at least three times. Results Optimal Condition for Electroporation of MDA-MB-468 Cells Cell type-specific effects of different pulse parameters were assessed. Square wave and exponential decay pulses were applied to MDA-MB-468 cells using the Gene pulser Xcell electroporation system.

2000; Binder et al. 2000; Scott et al. 2000; Davis and Johnsrude 2003; Narain et al. 2003; Rodd et al. 2005; Andics et al. 2010; DeWitt and Rauschecker 2012). Localization of such language-sensitive regions in BKM120 individual brains is important for both research

and clinical purposes, for example, when studying subtle linguistic contrasts (Ben-Shachar et al. 2003, 2004), developmental populations (Wilke et al. 2006; Rauschecker et al. 2009; Ben-Shachar et al. 2011), and in presurgical mapping (Swanson et al. 2007; Chakraborty and McEvoy 2008; Kipervasser et al. 2008; Bick et al. 2011). Localizing speech responses in an individual participant using Inhibitors,research,lifescience,medical functional magnetic Inhibitors,research,lifescience,medical resonance imaging (fMRI) is complicated by several factors. First, particularly along superior temporal regions,

cortical responses to sensory and linguistic aspects of speech are tightly packed, making it difficult to isolate responses to linguistic aspects of speech from primary auditory responses (Scott and Johnsrude 2003). Delineating language responses according to anatomical Inhibitors,research,lifescience,medical markers is further complicated by known individual variability in the mapping between cytoarchitectonic areas and gross anatomy (Amunts et al. 2000; Rademacher et al. 2001). An effective solution to these problems is to use a functional localizer to isolate speech-specific Inhibitors,research,lifescience,medical responses, by contrasting speech responses against responses to an auditory

baseline. In this article, we discuss the considerations in choosing such a baseline, and compare the localizing value of two widely used baselines for auditory speech processing. A functional localizer is a short fMRI scan which Inhibitors,research,lifescience,medical is added to the scan protocol in order to identify the individual’s regions of interest (ROIs) (Fedorenko et al. 2010; Saxe et al. 2006). For example, in the visual domain, ROIs such as V1, V2, hV4, and so on are typically identified in individual participants using retinotopy scans (Engel et al. 1994). Similarly, regions sensitive to visual faces Fossariinae and words are often localized by contrasting face versus house stimuli and words versus checkerboards, respectively (Kanwisher et al. 1997; Cohen et al. 2000; Duncan et al. 2009). In the context of speech processing, an optimal functional localizer aims to satisfy the following constraints: (a) Efficiency: Short scan, about 3–5 min long. This is most important in developmental and clinical populations; (b) Sensitivity: Evoke robust BOLD signals in each person’s speech-selective regions to allow ROI definition at the individual level; (c) Specificity: Isolate speech responses from other sensory and cognitive components.