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The excess of affected males with LDs identi- abnormalities of the microstructure of the planum tempor- fied in clinic and referred samples disappears in research- ale from autopsy studies generic 40 mg furosemide with visa blood pressure medication images, but conflicting data emerge cheap furosemide 100mg blood pressure chart heart.org, possi- based samples (25) cheap nasonex nasal spray on line. Although most studies implicate abnormalities in left temporal-parietal ana- tomic areas, additional findings have identified white mat- NEUROIMAGING ter, right hemisphere anomalies, motor cortex, cingulate gyrus, and the splenium of the corpus callosum. The neuroanatomic and functional pathways in the brain One of the older controversies regarding the functional involved in LDs were greatly clarified in the 1990s by a brain basis of dyslexia is whether dyslexia represents a visual variety of neuroimaging techniques. Reviews of neuroimag- (orthographic) disorder or a language-based (phonologic ing of LDs describe rapid progress in identifying the brain processing) disorder. Neuroimaging studies now appear to regions and functional pathways involved (20,26–29). NEUROIMAGING IN LEARNING DISORDERS Study Method Subjects Results Klingberg et al. White matter diffusion anisotropy in the temporoparietal region of the left hemisphere was significantly correlated with reading scores within the reading-impaired adults and within the control group. The anisotropy reflects microstructure of white matter tracts, which may contribute to reading ability by determining the strength of communication between cortical areas involved in visual, auditory, 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.

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Given the known role of subcortical networks as These studies have also shown adults with ADHD to be modulators of prefrontal functioning buy discount furosemide 100 mg online heart attack or anxiety, the term frontosubcor- impaired in other functions known to affect children with tical seems appropriate for ADHD purchase furosemide 40 mg otc arteria costa rica. These include the following: perceptual-motor behavioral or cognitive dysfunction that looks 'frontal' but speed as assessed by the digit symbol/coding tests (54 adalat 20 mg low cost,55); may be influenced by subcortical projections. For example, the cingulate cortex influences mo- Test (57,58). Because neuropsychological tests are free of tivational aspects of attention and in response selection and the potential biases of self-reported symptoms, the finding inhibition. The brainstem reticular activating system regu- that the neurocognitive profiles of adults with ADHD are lates attentional tone and reticular thalamic nuclei filter in- similar to those of children with ADHD suggests that the terference. Working memory deficits implicate a distributed diagnosis of ADHD is valid as applied in adulthood. Moreover, the atten- literature, not findings that have been consistently repli- tional problems of children with ADHD may implicate a cated. Although there are inconsistencies among studies, it wider distribution of neural networks. A system mainly in- is notable that the pattern of deficits that has emerged is volving right prefrontal and parietal cortex is activated dur- similar to what has been found among adults with frontal ing sustained and directed attention across sensory modali- lobe damage. The inferior parietal lobule and superior temporal support the hypothesis that the frontal cortex or regions sulcus are polymodal sensory convergence areas that provide projecting to the frontal cortex are dysfunctional in at least a representation of extrapersonal space and play an impor- some children with ADHD. Because neuropsychological tests provide indirect mea- sures of brain function, we must be cautious in using them Neuroimaging Studies to make inferences about the locus of brain impairment in ADHD. Yet because many of these tests have been standard- Fortunately, hypotheses based on neuropsychological infer- ized on normative populations and administered extensively ence can be tested with neuroimaging paradigms. Because to brain-damaged populations, observed deficits tests can neuroimaging studies provide direct assessments of brain Chapter 43: Pathophysiology of ADHD 581 TABLE 43. STRUCTURAL NEUROIMAGING STUDIES OF ADHD Study Diagnosis Method Findings Shaywitz et al. First, and adults with ADHD that used computed tomography the adolescent samples studied may have been more hetero- or magnetic resonance imaging. Among these studies, the geneous than the adult samples. Although all the adults had most consistent findings implicated frontal cortex, usually persistent ADHD, some of the adolescent cases may have limited to the right side, cerebellum, globus pallidus, cau- remitted by adulthood. Thus, frontal dopaminergic hypoac- date, and corpus callosum. Several other regions were less tivity may be associated with persistent ADHD only. Consistent with these findings, the natively, Ernst et al.

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With fMRI buy generic furosemide 100mg on line blood pressure medication that does not cause joint pain, the TMS coil can produce motor and vision areas order furosemide 100mg free shipping arrhythmia classification, TMS does not produce easily viewed both static and dynamic artifacts discount micardis generic. Although it may be possi- effects, so that this direct functional approach becomes im- ble to correct for the static effects, as in PET, some groups possible. The movement elicited by the TMS a train of pulses (56). Both mechanical and pneumatic sys- is a reassuring, if somewhat imprecise, way of being certain tems have been developed to do this. Although it minimizes that one is in the correct area. However, even with compara- the potential impact of the artifact, mechanically moving ble visible movement, one can be on one side or the other the TMS coil produces shimming and alignment issues on of the target area, and it is difficult to know how much or its own and does not allow for true interleaved imaging in how little additional stimulation is occurring. The dynamic artifacts produced by TMS within method reliably causes activation in large corticospinal cir- an fMRI scanner are both more complicated and more diffi- cuits, we have used the functional behavioral approach for cult to account for (see Fig. Substantial progress has been made, so that this cortex (51,52). Whichever method of locating the site of stimulation is used, it is important that the TMS coil be positioned accu- rately and repeatably, and then held securely in place so Integration of Temporal Domains of the that its position relative to the brain is maintained through- Scanner and Transcranial Magnetic out the stimulation. Each group seems to have developed Stimulation its own mounting systems. We have developed a system for accurately and repeatably positioning the TMS coil within The final picture produced by each of the functional imag- an MRI scanner (53). Both structural and functionally ing tools represents summed brain activity over a measure 30: Measuring Brain Connectivity 399 A TMS pulse Fat saturation pulse 90˚ Excitation pulse Read gradient x 100 Ringdown x 100 B C FIGURE 30. Researchers at the Medical University of South Carolina have recently developed the technique of performing transcranial magnetic stimulation (TMS) within the bore of a conven- tional 1. This process produces dynamic TMS-induced eddy currents (B) and static TMS-induced eddy currents (C). As seen in (B), these dynamic eddy currents are approximately twice as strong as the read gradient for about 20 milliseconds, and then drop to approximately the same size as the read gradient for another 20 milliseconds. Although the major eddy currents have died out by 40 to 50 milliseconds after the TMS pulse, some longer, low-level currents are still present that cause significant image artifact (C). The averaged time domain ranges from 20 to 30 Steady State minutes for FDG PET, to 40 to 60 seconds for 15O PET Inthismodel,researchersperformTMSthroughoutanentire and perfusion SPECT, to 2 to 3 seconds for BOLD fMRI, scan and then compare results with those of another scan in to milliseconds for EEG and electromyography. The actual which all conditions are the same except for the TMS.