This site welcomes original publications, review articles, case records in the field of neurology, psychiatry, neuroradiology, neuropathology, and neurosurgery
The author: Professor Yasser Metwally
http://yassermetwally.com
INTRODUCTION
February 7, 2010 — This section focuses on data pertaining to generalized anxiety disorder, obsessive-compulsive disorder, panic disorder, and posttraumatic stress disorder (PTSD).
Volumetric MRI has been used to show that adolescents who have generalized anxiety disorder have larger white matter and gray matter volumes in the superior temporal gyrus. [1] A right greater than left asymmetry also was noted in this structure and the percent of asymmetry correlated significantly with child report ratings on the Screen for Child Anxiety Related Emotional Disorders scale. This finding is suggestive of structural changes developing early on in the disease process. It remains to be seen whether or not they occur pre-morbidly.
Functional MRI has been used to evaluate intolerance to uncertainty, a major component of generalized anxiety disorder, panic disorder, and obsessive-compulsive disorder. Intolerance to uncertainty correlates positively with bilateral activation of the insula. [2] It may be that increased affective response to situations with uncertain outcomes with corresponding activation of the insula is a trait marker for certain anxiety disorders.
In this area, the data are approaching greater clinical usefulness in that prediction of response to treatment has been demonstrated. In adults who had generalized anxiety disorder, response to venlafaxine was predicted by greater pretreatment reactivity to fearful faces in the rostral anterior cingulate cortex and lesser reactivity in the amygdala as measured by functional MRI. [3] In children and adolescents who had generalized anxiety disorder, this modality was used to predict response not only to medication but also to cognitive behavioral therapy. [4] In this group there was a significant negative association between degree of left amygdala activation and measures of post-treatment symptom improvement.
Disordered caudate nuclear metabolism has long been implicated in the pathophysiology of obsessive-compulsive disorder. [5] In general, alterations of frontostriatal circuitry have been found in various studies. It has been suggested that discordant findings may be the result of different subtypes of the disorder (hoarding, germ phobia, and so forth) with different neurobiologic underpinnings.
Voxel-based morphometry has been used to show significantly lower gray matter density in pediatric obsessive-compulsive disorder patients compared with healthy control subjects in the left anterior cingulate cortex and bilateral medial superior frontal gyrus. [6] When compared with their unaffected siblings, patients displayed significantly greater gray matter volume in the right putamen. In adults, this technique has demonstrated that the dorsal cortical regions of healthy control subjects have significantly greater gray matter volumes than that of patients who have obsessive-compulsive disorder and that in the midbrain bilaterally this relationship is reversed. [7] Furthermore, greater total obsessive-compulsive symptoms were highly significantly related to larger gray matter volumes in the bilateral midbrain.
Response to treatment has been another fruitful area of investigation in obsessive-compulsive disorder. Recently, F18-flourodeoxyglucose (FDG)–positron emission tomography (PET) was used to demonstrate efficacy after only 4 weeks of intensive individual cognitive behavioral therapy. [8] Patients showed significant bilateral decreases in normalized thalamic metabolism and, unexpectedly, an increase in right dorsal anterior cingulate cortex activity that correlated strongly with degree of symptom improvement. It has been postulated that response to intensive cognitive-behavioral therapy may require activation of the dorsal anterior cingulate cortex because of its role in reassessment and suppression of negative emotions.
PTSD has proved another fruitful area in the neuroimaging literature. Several factors may have a bearing on the outcomes, including the type of trauma (eg, physical, sexual, or psychologic), the brain’s maturational stage at the time of the trauma, and the possibility of predisposing vulnerability. Over the past decade, consensus has arisen regarding the role of the amygdala, medial prefrontal cortex, and hippocampus in PTSD. [9] Specifically, amygdala responsivity is positively associated with symptom severity whereas that of the medial prefrontal cortex is inversely associated with the same. The hippocampus in PTSD has been shown to possess decreased volumes and deficiencies in neural and functional integrity.
Recent structural imaging has shown that children who have maltreatment-related PTSD had significantly smaller cerebellar volumes compared with healthy control subjects. [10] Furthermore, cerebellar volumes negatively correlated to the duration of trauma and positively correlated with age of onset of trauma. This adds to the consensus regarding the cerebellums importance in cognitive and emotional development.
Another pediatric study has yielded insights into the complex interplay of stress and developmental damage to the brain. Baseline cortisol levels and PTSD symptoms predicted hippocampal reduction in 15 children over an ensuing 12- to 18-month interval. [1] This is some of the earliest human evidence confirming preclinical data that the glucocorticoids secreted during stress can be neurotoxic to the hippocampus.
A unique group of Vietnam War veterans has afforded the opportunity to assess whether or not the characteristic findings of PTSD reflect the underlying cause or a secondary effect of the disorder. Veterans who had suffered brain injury and emotionally traumatic events exhibited a reduced occurrence of PTSD if they had damage to the ventromedial prefrontal cortex or the anterior temporal area that included the amygdala. [12] This suggests that these two structures are critically involved in the pathogenesis of PTSD.
The interaction of PTSD with other pathologic states also has been addressed. Blood oxygenation level–dependent functional MRI has been used to show reduced pain sensitivity in male veterans suffering from PTSD. [13] Compared to veterans matched for age and region of deployment, patients revealed increased activation in the left hippocampus and decreased activation in the ventrolateral prefrontal cortex bilaterally and in the right amygdala in response to nociception. The patients also rated fixed-temperature noxious conditions as less painful than did control subjects.
Reflecting on the anxiety disorders in general, it has been suggested that fear is a major component and that the amygdala is critical for the acquisition and expression of that emotion. It is hypothesized, however, that it is activity in the prefrontal cortex that controls what individuals who have an anxiety disorder ultimately experience. [14] PTSD, panic disorder, and the phobias—those disorders involving intense fear—seem characterized by underactivity in the prefrontal cortex, thereby disinhibiting the amygdala. Conversely, disorders involving worry and rumination—generalized anxiety disorder and obsessive-compulsive disorder—seem characterized by overactivity of the prefrontal cortex.
References
February 7, 2010 — Psychotic symptoms consist of delusions and hallucinations and may be present in a variety of conditions, including disorders of mood and cognition. This post focuses primarily on the data relating to schizophrenia, the most prevalent of the psychotic disorders. Despite falling under one diagnostic category, there likely are many etiologic subgroups subsumed within the diagnosis of schizophrenia.
Reduced cortical volumes and enlarged ventricles are long-established findings in schizophrenia. Recent studies have a focus on functional neuroanatomy. Volumetric MRI was used to investigate entorhinal cortical volumes in a large cohort of patients who had schizophrenia compared with normal control subjects. [1,2] Those afflicted were shown to have statistically significant smaller entorhinal volumes, particularly on the right side. This may play a major role in the cognitive disturbances found in the disease.
Changes in the adolescent brain over the first few years after first-episode psychosis was studied using MRI. Gray matter loss in the frontal cortex was significantly higher in male patients compared with control subjects—2.9% on the left and 2.0% on the right. [2] Additionally, male patients showed a higher rate of CSF volume increase in the left frontal lobe than control subjects. The lack of significant findings in female adolescents may have been the result of the study being underpowered to detect changes in this group. A similar study in adults found 3% reductions in whole-brain gray matter and 3.65% reduction in frontal lobe gray matter. [2]
More advanced analytic techniques also are providing answers. For instance, surface-based morphometry has delineated pathology in the anterior cingulate cortex of first-episode schizophrenia patients that previously was equivocal with the traditional volume-based approaches. [3] Relative to control subjects, patients had a bilateral reduction in thickness of the paralimbic regions of the anterior cingulate cortex and an increased surface area of limbic and paralimbic anterior cingulate cortex.
Cognitive dysfunction in schizophrenia has been studied with functional imaging. Functional MRI has shown that relative to control subjects, patients who have schizophrenia have a significantly stronger activation pattern in the frontoparietal network and hypoactivation in the thalamus during executive information manipulation. [4] Conversely, there was lower activation in the prefrontal cortex and anterior cingulate gyrus during stimulus encoding. This suggests that a deficit during encoding is driving altered activation during executive control.
One study used functional MRI to investigate the misattribution of speech as a contributor to auditory hallucinations. [5] Patients who had schizophrenia and auditory hallucinations were compared with patients who had schizophrenia but no auditory hallucinations and to matched normal control subjects. Compared with the two other groups, the hallucinatory group had altered activation in the superior temporal gyrus and anterior cingulate. These patients also made more external misattributions.
February 7, 2010 — Radiological quiz
Online radiological quiz. What is your diagnosis
Click to download the answer in PDF format
Click to download slide show in PDF format
February 6, 2010 — Radiological quiz
Slide show 1. What is your radiological diagnosis
Click here to download the answer in PDF format (1930 KB)
February 6, 2010 — Case record: Parasagittal meningioma
Online case record. Parasagittal meningioma
Click here to download the case record in PDF format (1930 KB)
Click here to download the short case version of this case record in PDF format (283 K)
