Loading

Kamagra Super

By A. Jensgar. College of Saint Mary. 2018.

The notable preclinical data of the effects that serotonin 5-HT1A agonists may potentiate the antipsy- of PTAC provide strong encouragement to examine the chotic activity of dopaminergic antagonists (328) discount 160mg kamagra super with amex. Activa- potential therapeutic effects of M2/M4 muscarinic agonists tion of inhibitory 5-HT1A autoreceptors may also counter- in schizophrenic patients order kamagra super 160 mg without a prescription. Among the agents that have been act the induction of EPS owing to striatal D2 receptor developed for the treatment of AD that are being examined blockade (329) 160mg kamagra super visa. Further, in schizophrenic patients, in- in schizophrenia are donepezil, metrifonate, galantamine, creased 5-HT1A receptor binding was seen in the prefrontal and xanomeline. Based on these preclinical data, com- pounds that act as serotonin 5-HT1A agonists are being developed as potential antipsychotic compounds. Glutamatergic Agents S-16924 is a novel, potential antipsychotic agent with The NMDA Receptor Hypofunction Hypothesis high affinity for dopamine D2/4, 1-adrenergic, and seroto- of Schizophrenia nin 5-HT2A receptors, similar to that of clozapine, in addi- tion to being a potent partial 5-HT1Aagonist (332). Reflect- Since the late 1950s, the anesthetics phencyclidine (PCP) ing its partial agonist actions at 5-HT1A receptors, it and ketamine have been known to induce 'emergence reac- attenuates cerebral serotonergic transmission, and preferen- tions' in 40% to 50% of individuals during the recovery tially facilitates dopaminergic transmission in mesocortical from anesthesia, that resembles some features of schizophre- as compared to mesolimbic and nigrostriatal pathways (333, nia (346). S-16924 exhibited a profile of potential antipsychotic early clinical studies and has demonstrated that subanes- activity and low EPS liability in animal behavioral models, thetic doses of ketamine can induce positive, negative, and similar to clozapine (332). In chronic stabilized schizophrenic patients, sub- Glycine is a positive allosteric modulator and obligatory anesthetic doses of ketamine can also exacerbate cognitive coagonist at the NMDA receptor (363) and this allosteric impairment and in some cases reproduce specific hallucina- regulatory site represents a potential target for drugs to aug- tions and delusional ideation remarkably similar to those ment NMDA-mediated neurotransmission. Both ketamine and PCP are potent non- the effects of noncompetitive NMDA receptor antagonists competitive NMDA receptor antagonists. There have been several clinical studies to test effects to a site within the calcium channel of the NMDA receptor of different glycine site agonists in patients with schizophre- complex, and thereby interfere with calcium flux through nia. The earliest studies in this regard used glycine in doses the channel. In more recent work with glycine, higher doses were are also psychotomimetic (350). The ability of NMDA an- administered (30 to 60 g per day) and more robust and tagonists to induce a spectrum of schizophrenia-like symp- consistent effects were found, primarily in the improvement toms has led to the hypothesis that hypofunction of NMDA of negative symptoms (241,367,368). Thus, at low dose of the amino acid, stimulatory responses are observed, but at higher doses, D-cycloserine blocks the effects of endogenous glycine. D- Antipsychotic Drug Actions in Relation to the cycloserine has been tested in patients with schizophrenia, NMDA Receptor Hypofunction and in a very narrow dose range, the agent was shown to The well-documented psychotomimetic effects of NMDA improve negative symptoms when administered alone antagonist in human suggest that effects of the drugs in (369), and when added to conventional antipsychotic treat- experimental animals could present useful pharmacologic ment regimes (240, 370). The 'inverted U'-shaped dose models of schizophrenia. In our recent studies, striking ef- response may result from the partial agonist properties of fects of subanesthetic doses of ketamine were observed on D-cycloserine, because antagonism of the actions of endoge- regional brain patterns of 14C-2-deoxyglucose (2-DG) up- nous glycine would be predicted at higher doses of the drug. Ketamine in- Interestingly, when D-cycloserine was administered in con- duces robust and neuroanatomically selective patterns of junction with clozapine, the negative symptoms of the pa- brain metabolic activation, with especially large effects ob- tients worsened (244,371). A ready explanation for these served in the hippocampus, nucleus accumbens, and medial effects is not available, but understanding the mechanisms prefrontal cortex (354,355). Pretreatment of rats with clo- involved in the worsening of negative symptoms after ad- zapine or olanzapine can completely block these effects of ministration of D-cycloserine to clozapine-treated patients ketamine (357,358). However, the typical antipsychotic may be an important clue in understanding the actions of haloperidol failed to antagonize the brain metabolic activa- both of these drugs. The poor penetration of the tion induced by ketamine (357). Similarly, clozapine and blood–brain barrier by glycine, and the partial agonistic olanzapine, but not haloperidol, effectively block NMDA properties of D-cycloserine, appear to make these agents antagonist-induced electrophysiologic responses (325), defi- less than optimal for providing pharmacologic agonism of cits in prepulse inhibition (359,360), and deficits in social the glycine regulatory site on the NMDA receptor (13). Thus, in a wide range of experimental D-serine is a full agonist on the strychnine-insensitive paradigms, atypical antipsychotic drugs selectively antago- glycine site of NMDA receptor (372) and is more permeable nize the consequences of experimentally induced NMDA than glycine at the blood–brain barrier, thus requiring a receptor hypofunction, raising the possibility that the thera- lower dosage. In a recent clinical trial, D-serine (30 mg per peutic effects of these agents may be associated with a similar kg per day) added to neuroleptic treatment in treatment- neurochemical action (362). These data, together with the results of If reduced NMDA receptor function is involved in the path- the clinical investigations with glycine and D-cycloserine ophysiology of schizophrenia, then drugs that enhance (346), offer promise for the therapeutic potential of enhanc- NMDA receptor function could be therapeutic agents and ing NMDA receptor function as a strategy for the pharma- potentially improve upon, or supplement, current antipsy- cotherapy of schizophrenia. Direct agonists of the NMDA recep- leagues (373) purified an enzyme from Type II astrocytes tor may not be feasible candidates in this regard, because that converts L-serine to D-serine. It may be that effectors of of the propensity of such drugs to produce excessive excita- this enzyme (directly or through possible receptor-mediated tion and seizures. Examining the effects of synthetic compounds membrane, and presynaptic group II metabotropic gluta- with greater potency and full agonistic activity at the glycine mate autoreceptor agonists (379–381). Administration of LY-354740, a group II metabotropic There are, however, no such compounds available for testing glutamate receptor agonist, blocked both behavioral activa- at present. In humans, Anand and co-workers (381) found that lamotrigine, a new anticonvulsant agent that inhibits gluta- Potentiation of NMDA Receptor Function by mate release, can reduce the ketamine-induced neuropsy- Inhibition of Glycine Uptake chiatric effects. These data suggest the possibility that gluta- mate release-inhibiting drugs (e. Although there is some controversy as to whether the glycine regulatory site on the AMPA/Kainate Receptor Antagonists NMDA receptor is saturated under physiologic conditions, The increased release of glutamate observed in response to recent data demonstrate that inhibition of glycine transport NMDA antagonist could mediate some of the behavioral by glycine transporter type 1 antagonist can potentiate elec- actions of the drugs by activation of non-NMDA receptors, trophysiologic effects of NMDA (374,375). Furthermore, including -amino-3-hydroxy-5-methy-isoxazole-4-propi- the glycine uptake inhibitor glycyldodecylamide attenuated onic acid (AMPA) and kainate receptors (377). In support PCP-induced hyperactivity more potently than glycine of the hypothesis that behavioral effects of NMDA antago- (364,376). These preclinical data suggest that inhibition nists relate to increased glutamate release, administration of of glycine uptake could represent a feasible approach to an AMPA/kainate receptor antagonist, LY-293558, par- potentiate NMDA receptor-mediated neurotransmission tially reversed impairment of working memory induced by and, possibly, treat schizophrenic patients. Furthermore, AMPA/kainate receptor antagonists reduce NMDA antago- nist-induced hyperlocomotion (383–385) and neurodegen- Glutamate Release-Inhibiting Drugs eration (386). These data suggest that AMPA/kainate recep- A number of studies have indicated that administration of tor antagonists may have utility for treatment of cognitive relatively low (subanesthetic) doses of NMDA antagonists deficits in which NMDA receptor hypofunction is suspect induces behavioral and brain metabolic activation in experi- (377). Consistent with these data, NMDA antagonists increase glutamate release in rats Potential of Positive Modulators of AMPA (377). In contrast to the increase in glutamate release by Receptors subanesthetic doses of ketamine, anesthetic doses of the drug decreased glutamate levels (377). The effect of differ- In apparent contrast to the postulated utility of AMPA/ ent doses of ketamine on glutamate levels is consistent with kainate receptor antagonists as antipsychotics, ampakines, our observations of increased 2-DG uptake in response to a class of compounds that allosterically enhance AMPA re- a subanesthetic dose, and reduction in 2-DG uptake in re- ceptor function, have also been suggested to represent po- sponse to an anesthetic dose of ketamine (354). Ampakines The stimulatory effect of NMDA receptor antagonism enhance excitatory (glutamatergic) transmission, facilitate presumably results from disinhibitory actions, perhaps by long-term potentiation, learning, and memory in rodents reducing excitatory input to inhibitory interneurons (362). In addition, preliminary results the glutamate-containing pyramidal cells (378), providing suggest that chronic administration of an ampakine (CX- support for the hypothesis that NMDA antagonism could 516) can improve negative and cognitive symptoms in schiz- result in excitatory effects by disrupting recurrent inhibitory ophrenia patients that also receive clozapine (284). Glutamate release can be inhibited by Na -chan- fects of positive and negative modulators of non-NMDA nel blockers, Ca2 -channel blockers, K -decreasing agents, glutamate receptors will be needed to clarify the potential toxins that prevent fusion of vesicles with the presynaptic of these compounds for treatment of schizophrenia (3). Long-term larger double-blind trials are crucially needed to Accumulating evidence from Manji and colleagues has iden- evaluate the efficacy of estrogen in conjunction with neuro- tified the family of protein kinase C (PKC) isozymes as a leptic treatment on psychotic symptoms in women with common target in the brain for the long-term action of the schizophrenia. Chronic treatment of rats with lithium or valproate induces a reduction in the levels of two PKC Dehydroepiandrosterone isozymes, and , in the frontal cortex and hippocampus, Dehydroepiandrosterone (DHEA) and its sulfate derivative as well as a reduction in the expression of a major PKC (DHEA-S) are neuroactive neurosteroids that represent ste- substrate, myristoylated alanine-rich C kinase substrate roid hormones synthesized de novo in the brain and acting (MARCKS), which has been implicated in long-term neu- locally on nerve cells (400). Although DHEA and DHEA- roplastic events in the developing and adult brain (391). In S are the most abundant circulating steroid hormones in view of the critical role of the PKC signaling pathway in the humans, their precise physiologic roles remain to be eluci- regulation of neuronal excitability, neurotransmitter release, dated. In humans, DHEA levels in blood rise dramatically and long-term synaptic events, Manji and associates postu- at puberty and sustain a monotonic decline with age, reach- lated that the attenuation of PKC activity might have anti- ing very low levels in late life. In a pilot study, they found marked anti- DHEA and DHEA-S enhance neuronal and glial survival manic efficacy of a potent PKC inhibitor tamoxifen, which and differentiation in mouse embryonic brain tissue cultures is also a synthetic nonsteroidal antiestrogen, in the treat- (401–403).

buy kamagra super 160mg lowest price

The antisense functional role of these new genes in processes related to oligonucleotide approach kamagra super 160mg without a prescription, however generic kamagra super 160 mg without prescription, has been plagued with stress and anxiety generic kamagra super 160 mg. Given this daunting task, methods for a number of issues regarding toxicity, and may therefore not more specific and long-term gene targeting will increasingly represent the optimal method for studying gene function in gain importance in neuroscience research aimed at uncover- vivo (162). One technique that is likely to be helpful is that of virally me- FUTURE DIRECTIONS diated gene transfer. In this method, a gene of interest is cloned into viral vector (with most of the viral genome Although the studies summarized in this chapter have con- removed to reduce toxicity and infection) and the modified tributed a great deal of knowledge about some of the genetic vector is then infused into a particular brain region using 896 Neuropsychopharmacology: The Fifth Generation of Progress standard stereotaxic procedures (see ref. Animal models in cognitive behav- Depending on the gene insertion and the selection of the ioural pharmacology: an overview. Acta to obtain either an increase or decrease in the amount of Psychiatr Scand Suppl 1998;393:74–80. Alternative phenotypes for allows for highly selective gene regulation and thus provides the complex genetics of schizophrenia. Biol Psychiatry 1999;45: a valuable new tool with which to study the effects of a 551–558. Cerebrospinal fluid corti- particular gene product on stress-related functioning. The cotropin-releasing hormone levels are elevated in monkeys with virally mediated gene transfer approach also has certain ad- patterns of brain activity associated with fearful temperament. Linkage of a any time or into any brain region, it results in a fairly robust neurophysiologic deficit in schizophrenia to a chromosome 15 locus. Chicago: University of Chicago it can be used to insert several genes at once in the same Press, 1972. Thus, the viral gene transfer approach completely 8. Responses of black-capped chickadees avoids the issue of developmental confounds, which are per- to predators. Predator model recognition and re- transgenic and knockout approaches. A few groups have sponse habituation in shoaling minnows. Acoustic characteristics of alarm calls associated down-regulation of discrete gene products related to neuro- with predation risk in chickadees. Anim Behav 1990;39: science research applications; the behavioral effects associ- 400–401. Interactions between tit flocks and sparrowhawks not appear to be associated with the high level of toxicity Accipiter nisus. Defensive behaviors in infant rhesus for stress-related psychopathology. On the clinical side, human genomic studies are indicat- Science 1989;243:1718–1721. Neurobiological correlates of the gene encoding CRH (170–172). Behav Phar- gresses, it will be interesting to see if particular mutations macol 1997;8:477–496. Measurement of method has been applied successfully to study the role of anxiety in transgenic mice. Defensive behaviors in infant rhesus monkeys: ontogeny and context-dependent selec- of polymorphisms in the gene encoding the 5-HT trans- tive expression. Clinically, one challenge will be to develop A, Harlow H, Stollnitz F, eds. The infant cry of primates: an evolutionary per- malities in genes that are believed to be related to stress and spective. Curr animal analogues of stress endophenotypes may provide a Protocols Neurosci 2000;2:8. Drug Design candidates for stress-related disorders. Fear and the brain: where have we been, and where crosstalk between animal studies and clinical findings. Are different parts of the extended amygdala involved combined efforts will undoubtedly facilitate our under- in fear versus anxiety? Neurobiological mecha- netic contributions to anxiety and stress-related disorders. Assessing the validity and vocalizations in animals: GABAA and 5-HT anxiolytics. Ethopharmacological studies of Chapter 62: Animal Models and Endophenotypes of Anxiety and Stress Disorders 897 anxiolytics and aggression. Eur Neuropsychopharmacol 1991;1: on transcriptional activity of inducible immediate-early genes, 97–100. Effects of buspirone on operant behavior in the hypothalamus of borderline hypertensive rats. Attenuation of the effects gene expression in the paraventricular nucleus are enhanced in of punishment by ethanol: comparisons with chlordiazepoxide. Link between emotional memory and correlates of behavioral inhibition in young children of parents anxiety states: a study by principal component analysis. A 3-year related behaviours and in sensitivity to diazepam in inbred and follow-up of children with and without behavioral inhibition. Psychopharmacology 2000;148: J Am Acad Child Adolesc Psychiatry 1993;32:814–821. The free-exploratory ioral inhibition in childhood: a risk factor for anxiety disorders. Social anxiety and history of behavioral mice compared to C57BL/6 mice. Infants and young children ogy of behavioral inhibition in children. Child Dev 1987;58: in orphanages—one view from pediatrics and child psychiatry. Psychological and neuroendocrinological in freezing and cortisol in infant and mother rhesus monkeys. Infantile experience and resistance to physiological induced behavioral inhibition in preweanling rats. Mother-infant relationships among free-ranging peraments in rhesus monkeys. Behav Neurosci 1998;112: rhesus monkeys on Cayo Santiago: a comparison with captive 286–292. Eur J Endocrinol 1999;141: Review of evidence: implications for research. Maternal separation in monkey infants: a model of 1994–95;1:251–257. Intracranial action of corticosterone releasing hormone related behavioral and neuroendocrine re- facilitates the development of behavioral inhibition in the sponses to stress in Lewis and Fischer rats.

buy kamagra super 160 mg on line

The opinion was formed that Mr F had been hoarding for years and that with the assistance of medication and supportive therapy he was now able to discard some of this material discount kamagra super 160 mg with amex. Mr F was aware that the psychiatrist would probably discard these belongings purchase kamagra super 160mg without prescription, he did not object cheap kamagra super 160 mg free shipping, he seemed unable to do so himself. After 4 years Mr F telephoned his psychiatrist that he was again feeling depressed. He said he could not come to an earlier appointment, and would not accept hospitalization. He did not arrive at his next appointment and was found in his unit of an overdose. Yale-Brown obsessive-compulsive scale (YBOCS) The YBOCS (Goodman et al, 1989) is the most commonly used OCD scale. However, it is protected by copyright an only the flavour can be here presented. There are two parts, 1) a symptom check list, and 2) a severity rating scale. The symptom check list has questions similar to the following: 1. Do you worry excessively about speaking or acting in a manner that you think is harmful, violent, sexually inappropriate, immoral, or sacrilegious? Do you repeatedly ruminate about unwanted thoughts in an effort to prove to yourself that you will not act in a manner that you think is harmful, violent, sexually inappropriate, immoral, or sacrilegious? Do you recite prayers or certain phrases in an effort to rid yourself of unwanted thoughts or to ensure that nothing bad happens? Do you often repeat routing, daily activities to ensure that you did not harm someone (e. Do you wash your hands or shower more often or for longer periods of time than most other people? Do you repeatedly visually check to be sure you have properly performed a just-completed task (e. Do you frequently ask others for reassurance that tasks have been properly completed (e. Do you repeatedly ask others for reassurance that you have not done something “wrong”, “bad”, or “harmful”? Do you unnecessarily arrange, order, or tidy the contents of your desk, closet, cabinets, bookshelves, etc, to make them symmetrical or “just right”? Do you unnecessarily straighten common household objects such as window blinds or rugs in an effort to make them symmetrical of “just right”? Do you repeatedly count mundane items that do not really merit counting (e. Do you have great difficulty discarding things that have no practical value and that most other people would consider rubbish (e. The severity rating scale is similar to the following: Item Range 1 Time spent 0 h/day 0-1 h/day 1-3 h/day 3-8 h/day >8 h/day on obsessions 0 1 2 3 4 2 Interference None Mild Definite but Substantial Incapacitating from manageable impairment obsessions 0 1 2 3 4 3 Distress None Little Moderate Severe Near constant, from but disabling obsessions manageable 0 1 2 3 4 4 Resistance Always Much Some Often Completely to resist resistance resistance yields yields obsessions 0 1 2 3 4 5 Control Complete Much Some Little No control over control control control control obsessions 0 1 2 3 4 Obsession subtotal (add items 1-5) _________ Pridmore S. Psychiatric Clinics of North America 2014; 37: 393-413. Incompleteness and not just right experiences in the explanation of obsessive-compulsive disorder. The familiality of specific symptoms of obsessive-compulsive disorder. Genetics of obsessive-compulsive disorder and related disorders. Psychiatric Clinics of North America 2014; 37:319-335. Examining the link between hoarding symptoms and cognitive flexibility deficits. Obsessive-compulsive spectrum disorders: a defensible construct? Australian and New Zealand Journal of Psychiatry 2006; 40:114-120. Not just right experiences and obsessive- compulsive features: experimental and self-monitoring perspectives. Prevalence of body dysmorphic disorder symptoms and body weight concerns in patients seeking abdominoplasty. Cognitive behavioral therapy of obsessive-compulsive disorder. Dialogues in Clinical Neurosciences 2010; 12: 199-207. Abnormal white matter structural connectivity in adults with obsessive- compulsive disorder. Cognitive-behavior therapy for adolescent body dysmorphic disorder. Long-term outcomes of obsessive-compulsive disorder: follow-up of 142 children and adolescents. Toward a neuroanatomy of obsessive-compulsive disorder. Genetic neuropathology of obsessive psychiatric syndromes. Canadian clinical practice guidelines for the management of anxiety etc. Dialogues in Clinical Neuroscience 2010; 12: 187-197. Recent advances in understanding and managing body dysmorphic disorder. Obsessive-compulsive disorder as a risk factor for schizophrenia: a nationwide survey. The neural correlates of obsessive-compulsive disorder: a multimodal perspective. DNA methylation at the neonatal state at the time of diagnosis: preliminary support for an association with the estrogen receptor 1, etc. Value-based decision making under uncertainty in hoarding and obsessive-compulsive disorders. Current issues in the pharmacological management of obsessive-compulsive disorder. Brain structural correlates of obsessive-compulsive disorder with and without preceding stressful life events.

discount 160mg kamagra super mastercard

The anisotropy reflects microstructure of white matter tracts cheap kamagra super 160 mg visa, which may contribute to reading ability by determining the strength of communication between cortical areas involved in visual discount kamagra super 160mg line, auditory buy kamagra super 160 mg cheap, and language processing. Dyslexics with a history of many symptoms of ADHD in childhood (high ADHD) accounted for the group differences in P300; the dyslexics with a history of few or no such symptoms (low ADHD) were indistinguishable from the controls at all electrode sites. The results are interpreted as suggesting that a distinct brain organization may characterize dyslexic men with a history of concomitant deficits in attention. In contrast, the letter-string–specific responses peaking around 150 ms predominantly in the left inferior occipitotemporal cortex in fluent readers were undetectable in dyslexic readers. Thus, while the early visual processing seems intact in dyslexic adults, the pattern of cortical activation starts to differ from that of fluent readers at the point where letter-string–specific signals first emerge during reading. Best and Demb, Sagittal magnetic resonance Dyslexics with documented Dyslexic subjects did not deviate from 1999 (32) images of PT and MC deficits and controls normal leftward PT asymmetry, magnocellular visual but both groups became less pathway left-lateralized with methods that excluded sulcul tissue. Results suggest that dyslexic subjects with a magnocellular deficit do not always have abnormal symmetry of the PT. PT symmetry may instead be related to a different subtype of dyslexia. In addition, PT asymmetry in any subject group depends on the measurement method. In contrast, no group main or interaction effects for the subcortical or callosal structures. No significant differences were observed in the nonlanguage tasks. These results preclude an explanation of deep dyslexia in terms of purely right-hemisphere word processing. These results support the separation of the reading disabled into a group that has difficulty translating orthography into phonology and a group that is slower functioning and has reduced capacity in preparing for a response. These results support a conclusion that the impairment in dyslexia is phonologic and that these brain activation patterns may provide a neural signature for this impairment. Given the heterogeneity of the dyslexic population, some subgroup of dyslexic individuals (i. However, anomalous asymmetry of the planum did not contribute to functional abnormalities demonstrated in these patients by positron emission tomography. No differences were seen in the anterior or middle corpus callosum. The increased area of the posterior corpus callosum may reflect anatomical variation associated with deficient lateralization of function in posterior language regions of the cortex and their right-sided homologues, hypothesized to differ in patients with dyslexia. This could be due to a dysfunctional left insula which may normally act as an anatomic bridge among Broca area, superior temporal, and inferior parietal cortex. The independent activation of the posterior and anterior speech areas in dyslexics supports the notion that representations of unsegmented and segmented phonology are functionally and anatomically separate. The leftward asymmetry is much reduced in patients with schizophrenia due to a relatively larger right PT than normal controls. ADHD, attention deficit hyperactivity disorder; fMRI, functional magnetic resonance imaging; MCA, middle cerebral artery; MHPG, XXX; MT, XXX; PET, positron emission tomography; PT, planum temporale; rCBF, regional cerebral blood flow; RD, reading disorder. Chapter 44: Learning Disorders 605 striate visual magnocellular pathways and specific phono- and early elementary years can reduce the overall rate of logic processing pathways in the left hemisphere are in- RDs (36,37) and can improve outcomes for children who volved in dyslexia, a finding possibly reflecting different are at high risk of RD (38,39). One metaanalysis reported subtypes at the behavioral level. As noted earlier, cognitive a combined effect size for phonologic awareness training of behavioral analysis suggests that distinctive mechanisms for 1. For example, in deep dyslexia, it is difficulty (40). Thus, a between normal and impaired readers appears to reflect the patient may read 'spirit' as 'whiskey,' or 'church' as difficulty many poor readers have in mastering phonologic 'priest. Torgesen exam- dyslexia, deep dyslexia may reflect a right-hemi- ined results from five large-scale early reading intervention sphere—based processing mechanism (31). Such findings point to the need language system, involving the segmentation and synthesis for the development of even more powerful intervention of phonemes (20), others find evidence that magnocellular techniques to facilitate the acquisition of early reading skills. As noted by Filipek, cognitive neurosci- phonologic awareness as a necessary, but not sufficient con- ence identifies specific computational tasks that should be dition for the development of skilled reading (15). Fluent used to provide more homogeneous samples at the behav- reading requires the development of orthographic reading ioral level for further advances in the neurobiology of devel- skills or the ability to recognize words by sight (41). For example, rather than using paired readers generally show deficits in this area that persist classic clinical criteria for dyslexia, which leads to samples into adulthood (41,42). Interventions to improve fluency with diverse subtypes, neuroimaging studies may do better are less well developed than interventions for the develop- to select samples by visual, lexical, and semantic criteria ment of decoding skills (i. The repeated readings technique, which involves mul- tiple readings of the same passages, is the most researched approach to improving fluency (43), and it has shown lim- EDUCATIONAL MANAGEMENT ited but positive effects on fluency (44). The increased atten- tion to issues of fluency in reading research has resulted in Various educational treatments have been developed for the development of new, comprehensive intervention ap- LD. In general, the most effective treatment approach is proaches that ultimately may be more effective than existing one that involves careful delineation of the specific academic techniques in addressing fluency deficits (23). At present, deficits evidenced by the child and intensive instruction in however, fluency deficits remain one of the most persistent the skill areas in which deficiencies are documented (34). Response to treatment varies by individuals, so it is impor- tant that careful monitoring take place throughout treat- Although most children with RDs show deficits in word ment to ensure that an intervention is effective for a particu- recognition skills, comprehension deficits are also common. In this section, we briefly summarize the These may occur alone or in the presence of impaired word educational treatment literature by academic area and then recognition skills (45). When impaired word recognition is summarize research related to treatment monitoring or the primary source of the comprehension deficit, decoding formative evaluation of interventions. However, interven- tions have also been developed to address comprehension Reading deficits directly. Two metaanalyses found substantial im- Considerable progress has been made in the development of provements for disabled readers who receive intensive in- preventive and early intervention approaches for beginning struction in reading comprehension (47,48). Several studies have demonstrated that explicit in- ies, metacognitive approaches (e. There were no improvements in composition skills Geary characterized research in the area of MDs as 'primi- in any of the treatment groups. Nevertheless, effective remediation techniques for MDs have been devel- oped. Slopes that do not differ from zero are an obvious Written Expression indicator of the need for a new treatment approach. How- Difficulties with composition and writing fluency are com- ever, estimates of typical response to treatment for students mon in children with LDs. Several researchers have shown with LDs are also available and can be used as a basis for that cognitive strategy instruction is effective in improving deciding whether a given treatment is producing sufficient the composition skills of children with written language progress (65). When formative evaluation strategies such as deficits (52–54). Generally, such interventions provide CBM are incorporated into treatment strategies, outcomes students with explicit instruction in thinking and problem- for students with disabilities improve markedly (66).