Brain Imaging

Obsessive Compulsive Disorder (OCD) is a antecedent characterized by recurrent intrusive, often repugnant, and always care-ridden thoughts and doubles and by sets of ritualized behaviors performed compulsively by the sufferer in an attempt to allay the anxiety. The compulsive behaviors typically turn in little relief, however, and the sufferer remains relegated to an anxious and painful daily get at a lower place ones skin.Thus, the diligent of who drives over the same speed bump distri exclusivelyively morning whitethorn find it impossible to relieve bingleself of the concern that one whitethorn consider, on a particular morning, driven over a pedestrian instead, and one is compelled to circle the block in a ritualized fashion searching for a crushed trunk in the street. While the sufferer is able to endorse the perverse and senseless nature of the rituals, this insight alone fails to relieve the experience of helplessness (Pauls et al. , 1995).As has been true of most psychiatrical unsoundnesss, traditional etiologic explanations afford been based on psychoanalytic findings and constructs. Formulations of the illness based on cognitive processing models represent a more recent development. Still more recently, a significant reconceptualization of neurotic symptomatology has followed the development of modern serviceable visualise technologies, and a biologically-oriented and star-centered view of OCD has emerged in light of the substantial findings from the last decades.The most popular superstar theory to date explains the pathogenesis of OCD as an imbalance in the action of a pair of interrelated neural circuits which, under popular circumstances, maintain one another in a state of useablely balanced tone. It may be p arenthetically added that, to the extent these encephalon entropy are themselves understood, it has become possible to evaluate psychological theories of OCD in functional terms (Robinson et al. , 1991). The neurobi ology of OCD has been a subject of research interest for several decades, with the put out having become increasingly formulated as a neuropsychiatric illness.Modern neuropsychiatric hypotheses curb been guided by data having its origins in data deductd from the acquit study of OCD patients victimization newly genuine non-invasive brain vision techniques. probatory findings from this area of inquiry are summarized in the following pages. Background to OCD OCD symptomatology has been report among patients with closed head trauma to the basal gangliar structures and among those with basal ganglia lesions demonstrable concomitant to carbon monoxide poisoning and to wasp sting (McKeon, 1984).Symptoms have additionally presented as a clinical feature both of striatal necrosis and facade lobe lesion (Siebyl et al, 1989). Thus, the sign background of data around OCD has regardd the basal gangliar structures, particularly the striatum, and, to a lesser extent, the head-on lobe. Imaging studies of the living brain are generally divisible into devil distinct categories, those representing morphologic or structural ab expressionity, on the one hand, and those representing disturbance of function at the cellular or metabolous aims, possibly with whole very small or wholly insensible flips in sound structure, on the other.The distinction is important while investigation at the level of structure and morphology bequeath reveal atrophic change or egregious pathology (eg. , tumor, trauma, etc. ,) investigation at the metabolic level provides a window removely into what has been termed, in traditional discourse, functional psychical illness. That is, structures which have retained their morphologic integrity may nonetheless be shown to be functioning in metabolically hyperactive or hypoactive state sex act to conventionality. In the interest of maintaining this important distinction, studies deriving from the two imagery modality sorts are review ed here sepa countly.Structural brain mental imagery studies Luxenberg, Swedo, Flament et al. (1989) use quantitative Computed Tomography (qCT) to analyze the morphologic playscripts of various brain structures believed cardinal in OCD. Clinical subjects with childhood-onset OCD were selected on the nates of active and unabated symptomatology of at least one year during their illness. While depressive symptomatology with onset subsequently obsessive illness was not an exclusion criterion, none of the patients was depressed at the date of the qCT examination.The researchers found that mean scissor-tailed marrow mass in the patients was significantly less than that of control subjects. No other significant brain abnormalities were found. Behar, Rapoport and iceberg lettuce, et al (1984), report on the administration of CT scans and neuropsychological mental test measures to 16 adolescents with OCD and 16 matched controls. Patients were found to have significantly increas ed ventricular coat ( telling to whole-brain gaudiness) and to show spatial-perceptual deficits on the Money Road Map Test of guiding Sense.The Money Map Test uses a simulated street office with a avenue indicated by a dotted line. The subject traverses the route and indicates a well(p) or left turn at each choice point. Near the midpoint of the examination the subject is required to mentally rotate himself in order to reverse his own serious-left reference. Patients with frontal lobe lesions have been reported to do poorly on this task. Subjects ventricular size and neuropsychological test findings were not significantly correlated, however, and the researchers suggest that significant co-morbidity at bottom the patient precedent led to unexpected results.In concomitant, the patient sample had been selected on the bum of its extraordinary psychiatric symptomatology It is possible that (the OCD subjects) are atypical in that magnanimous patients comm exclusively report b eing able to conceal their symptoms after top off onset in childhood (Behar, Rapoport and Berg, et al. , 1984, p. 365). The results of the Behar study are also at odds(predicate) with those of Insel and associates (1983), who report neither ventricular blowup on CT brain image nor significant neuropsychological deficits on the Halstead-Reitan battery of neuropsychological tests in 18 adult OCD sufferers.Confirmation for ventricular enlargement is likewise not discover in the present majority of structural brain studies. Garber, Ananth, Chiu, and colleagues (1988) performed Magnetic plangency Imaging (MRI) scans on 32 patients meeting the DSM-III criteria for OCD in an investigation of the bobtail and ventricular findings. Subjects were judged free of psychological medicine other than OCD on the basis of psychiatric testing and evaluation, and severity of OCD symptoms was rated at the duration of MRI by heart and soul of the Yale-Brown Obsessive-Compulsive Scale.MRI creates highly detailed anatomical images using radiofrequency resonance signals raise from the hydrogen atoms of tissue under study. The technique produces structural images which are in m all respects (eg. , spatial root) quite superior to those provided by CT (Garber et al. , 1988). Further, a technical routine known as spin-lattice relaxation time (or Tl), in which a summary measurement of the time required for protons disturbed within host molecules to relax to baseline is taken as a direct measurement of the mobility of water protons in membranes and fluids.In the study with OCD patients, Behar and colleagues discovered significantly lengthier corrected Tl values for clinical subjects congenator to controls in the convex nuclei and the right frontal lobes white matter. Because of the high degree of heterogeneousness in both samples, subgroups within the clinical sample were developed on the basis of family account and medication status and analyzed against one another. No surro unded by group differences were noted based on medication status.Patients with family histories of OCD differed from those with no such histories in the anterior cingulum, showing significantly legal briefer Tl values. No gross structural differences were specific to the OCD group. Garber and colleagues (1988) ascribe the altered Tl include to insidious atrophy in the right frontal pallium or vitiated line of merchandise menstruate to this portion, corresponding to a decline in frontal cortical metabolism. Involvement is also suggested on the parts of the cingulate gyms and lenticular nuclei.These areas are components of frontal-limbic pathways that may mediate the symptoms of obsessive-compulsive disorder surgical alteration of the relationships among structures within these pathways have produced symptomatic improvements. Moreover, the authors propose that hereditary influences on the illness may be most directly expressed in the cingulate region. The implication of the fron tal lobes and cingulate gyms in OCD suggests abnormalities in cortical-striatal-thalamic-cortical circuits.Robinson, Wu, and Munne et al. (1995) employ MRI in a structural volumetric analysis of selected brain regions within or adjacent to these circuits in 26 patients with OCD (DSM-VI-R criteria). While subjects were screened for a number of exclusionary criteria, co-morbidity with depression was not among these. twenty-six screened normal control subjects were matched to the OCD patients. In results which directly contradict those of Scarone, Colombo, and Ambruzzese, et al.(1992), in which right tail-shaped nucleus size was found by MRI to be increased in patients with OCD, Robinson and colleagues report a significantly diminished morphometic volume for the caudate nuclei isobilaterally. These findings are consistent with those of Luxenberg et al. (1988), described above, in which morphometric analysis by CT indicated significantly decrease caudate nucleus volume in patients w ith OCD. Study by Alyward, Schwartz, and Machlin et al. (1991) report no statistically significant differences amidst OCD and normal subjects on MRI studies of caudate volume.Their report demonstrates a direct correlation in patients with OCD between the putamen volume and the Global Severity of psychopathology earn developed by the National Institute of Mental health as well as between the caudate volume and the Hamilton clinical depression Rating Scale score, but found no correlations with the Y-BOCS total score or with the obsessions or compulsions subscore on this instrument. Curiously, however, division of the patients with OCD into subgroups based on a history of depression did not demonstrate a significant difference.Imaging measures were kindred between subjects with and without medication histories. There was no evidence of ventricular enlargement in patients with OCD. As a group, studies of brain morphology and structure have returned advantageously inconsistent find ings in OCD particularly differing are reports on the caudate nucleus and striatal region. Different study methods and small sample sizes may poster partially for these discrepant findings and represent problems which must ultimately be dominate before a valid consensus can be reached.The significant preponderance of OCD symptomatology within neurologic populations and its high co-morbidity with depression endure to the potential for heterogeneity in OCD samples (Pauls, 1995). The Alyward finding of increased caudate volume in OCD subjects with higher(prenominal) depression scale scores, but not among OCD subjects at large, not only reveals the heterogeneity of the disorder but illustrates the necessity of roughnessously defining sample parameters before meaningful comparison and replication may be undertaken.Such rigor has not insofar been sufficiently applied in structural imaging studies. Notwithstanding these issues, the question of a chronic degenerative process with resu ltant role caudate diminution over time is suggested by certain of the data, in particular light of the fact that most of the OCD patients study by the Robinson and Luxenberg groups were longtime(prenominal) sufferers. Longitudinal follow-up studies would be needed to determine whether caudate volume changes in OCD are modernized.Additionally, because structural brain imaging modalities are bare-assed only to pathology which has resulted in physical change in tissue, they omit term of metabolic or functional change. The following section offers a countersign of imaging findings based on functional processes of the brain modalities of this type substantially enlarge the data available from structural imaging alone. Functional brain imaging studiesFunctional brain imaging refers collectively to that set of techniques used to derive images reflecting biochemical, physiologic, or electrical properties of the central nervous system (Devous, 1995). The most developed of these techniq ues have in common the registration of such data in digitized maps which thus represent visually to the diagnostician or researcher the sexual relation metabolic activations among brain structures of interest (provided that the dimensions of these lay within the spatial resolution capability of the particular technique).The maps can typically be rendered in every standard anatomical plane for the sake of further clarifying these metabolic relationships. Positron electric discharge Tomography (PET), so named for the species of radioactive decay on which it depends, and the more economical and widely available modality of Single Photon Emission Computed Tomography (SPECT) each registers in a digitized functional map relative regional metabolic activations for any given brain state (eg. , under challenge, during active symptomatology, at rest, and so forth).SPECT maps the distribution of a radioactively labeled pharmaceutical administered intravenously administered to a subject and ty pically designed to incorporate itself into brain ancestry flow processes in a manner pressman to the relative activations of the latter (Devous, 1995). The emission of gamma radiation from the agent after it has been allowed to incorporate itself into brain tissue enables the subsequent mapping of blood perfusion densities crosswise cortical regions with the use of SPECT imaging hardware.Blood flow and metabolism are tightly coupled within the brain under most normal and pathological circumstances, and on that pointfore inferences about neurometabolism are accurately informed by measures of relative blood flow (Devous, 1995). One of the more popular radiopharmaceuticals for such blood flow mapping is referred to generically as HMPAO, an acronym for the chemical structure of the agent. abut to this chemical structure is the radioactive element Technetium-99m, which is favored as an imaging isotope because of its half-life and energy characteristics (Devous, 1995). two facts of brain function are pertinent to any review of imaging studies in this area. The first of these requires the reader to keep in mind that an activated cortical region may be restrictive or excitatory. In the basal ganglia system, for example, excitatory and inhibitory input sf contribute mutually to a functionally balanced neural tone. The second fact is closely related A system which lies efferent to the hypermetabolic one will correspond to the nature of this input Inhibitory or excitatory.Notwithstanding the complexities connected to image interpretation, the functional modalities have permitted the development of a more conclusive body of evidence regarding brain function in OCD than has been the case with structural imaging modalities. A consensus has emerged around increased activity in the right orbitofrontal cortex (OFC). Less agreement exists with respect to the role of the striatum and associated basal gangliar structures. Rubin, Villanueva-Meyer, and Ananth et al.(1995) canvas ten adult male patients with OCD and ten age-matched adult male normal controls using SPECT Patients with OCD had significantly increased pulmonary tuberculosis of the metabolic tracer radionuclide in the high dorsal parietal cortex bilaterally, in the left posterofrontal cortex, and in the orbital frontal cortex bilaterally The patients also had significantly reduced tracer uptake in the head of the caudate nucleus bilaterally, but not in the putamen or thalamus, consistent with the hypothesized reduction of caudate nucleus activity in OCD. Baxter, Schwartz, Maziotta et al.(1992) reports findings which conflict with those of Rubin and co-workers on the activation of the caudate nuclei. In the Baxter study, ten non-depressed OCD patients were compared with ten age- and gender-matched normals using PET scans. Subjects were screened for current co-morbidity with major depression, bipolar disorder, cyclothymic disorder and dysthymia. All but two subjects had suffered from depre ssive disorders in the past. analogy of the scans indicated that patients with OCD had significantly higher overall glucose metabolic rate values than normal controls.Orbital gyri were significantly higher in metabolic activation bilaterally, as were the bilateral heads of the caudate nuclei. As described, Rubin et al. (1995) report diminished metabolic activity in the head of the caudate nuclei bilaterally. Machlin, Harris, and Pearlson, el al. (1991) found elevated blood flow in the anterior cortex and cingulate (termed the medial-frontal region) in ten OCD patients studied with SPECT relative to a matched sample of eight normals.Several other well-conceived functional imaging studies implicate the structures of both the Papez circuit and Modells hypothesized fronto-striatal-pallido-thalamic-frontal loop. Swedo et al. (1989) compared 18 OCD patients and 18 normals using PET, and while no whole-brain glucose metabolic differences were found between groups, the left orbitofrontal, right sensorimotor, and bilateral prefrontal and anterior cingulate regions were notably higher in adults with childhood-onset OCD. Within this group, a substantiative correlation emerged between glucose uptake in the prefrontal and orbitofrontal regions and state measures of anxiety.In addition, responders to sermon with clomipramine were distinguishable from non-responders on the basis of regional changes in the right cingulate and right orbitofrontal regions, with response failures evincing significantly higher pre-therapy activations. Baxter et al. (1992), in a series of studies with a total of 24 adult patients with OCD, found increased FDG uptake in the cerebral hemispheres overall, and in the orbital gyri and caudate nuclei in the OCD group as compared to normal controls.Rubin, et al (1995) used SPECT imaging and found elevated uptake in the dorsal parietal cortex bilaterally, the left posterofrontal cortex and the OFC bilaterally. The group also found decreased uptake in the heads of the caudate nuclei bilaterally. Two diametric comparisons have been made of OCD subjects before and after symptom aggravation. Rauch et al. (1994) used oxygen-15 labeled carbon dioxide PET to study individually tailor-made provoking stimuli in order to provoke symptoms in eight patients with OCD.Paired comparisons pre- and post-challenge yielded an increase in regional Cerebral Blood Flow (rCBF) in the right caudate nucleus, left anterior cingulate cortex, and also bilaterally in the OFC subsequent to challenge. McGuire et al. (1992) studied four OCD patients during actual exposure to contaminants in a pattern tailored individually to produce successively greater degrees of anxiety. rCBF was found to increase in the OFC, neostriatum. globus pallidus, and thalamus in relation to the urge to perform compulsive movements.These two diametrical comparisons of patients pre- and post-challenge provide a unique opportunity to examine differences between a resting and an obs essional state in the same patient during a brief period. Further, such an examination sheds light on the manner in which inconsistencies among functional imaging studies may be due to variations in the mental state of obsessional patients at the time of the imaging studies. While the architecture of the anxiety challenge varies considerably between the Rauch and McGuire protocols, it remains nonetheless close towhat thwart that more consistent findings are not elicited in the paired comparisons.In these studies, as in the literature more generally, substantial disagreement exists on the response of the cingulate cortex and caudate nuclei. It is noteworthy, however, that the two paired challenge studies hold up with respect to the hyperactivated state of the OFC. It is on the issue of striatal, specifically caudate, activation and morphology that most disagreement exists across both the structural and functional brain imaging studies. It is possible to speculate on the cause of t his inconsistency caudated metabolism may be a state, rather than a trait, cross in OCD.It may also be that pathology in this region is progressive Subjects with damaged striatal mechanisms may, for instance, manifest a hypermetabolic condition in the region for some lengthy period before an atrophic process ultimately begins and results in the opposite finding, hypometabolism and volumetric diminution over a period of time. unity across subject samples in terms both of length and history of illness and co-morbidity with other pathology is therefore essential to further investigation of this region in OCD. ConclusionThe two categories of imaging study at times scoop up roles along a continuum of pathological severity or etiology. For example, a degenerative change in tissue density or overall size and shape may have developed only after a lengthy period of metabolic dysregulation. 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