Vincent P. Mathews

Activity and connectivity of brain mood regulating circuit in depression : A functional magnetic resonance study

BACKGROUND Functional imaging studies indicate that imbalances in cortico-limbic activity and connectivity may underlie the pathophysiology of MDD. In this study, using functional Magnetic Resonance Imaging (fMRI), we investigated differences in cortico-limbic activity and connectivity between depressed patients and healthy controls. METHODS Fifteen unmedicated unipolar depressed patients and 15 matched healthy subjects underwent fMRI during which they first completed a conventional block-design activation experiment in which they were exposed to negative and neutral pictures. Next, low frequency blood oxygenation dependent (BOLD) related fluctuations (LFBF) data were acquired at rest and during steady-state exposure to neutral, positive and negative pictures. LFBF correlations were calculated between anterior cingulate cortex (ACC) and limbic regions--amygdala (AMYG), pallidostriatum (PST) and medial thalamus (MTHAL) and used as a measure of cortico-limbic connectivity. RESULTS Depressed patients had increased activation of cortical and limbic regions. At rest and during exposure to neutral, positive, and negative pictures cortico-limbic LFBF correlations were decreased in depressed patients compared to healthy subjects. CONCLUSIONS The finding of increased activation of limbic regions and decreased LFBF correlations between ACC and limbic regions is consistent with the hypothesis that decreased cortical regulation of limbic activation in response to negative stimuli may be present in depression.

Recommendations for Imaging of Acute Ischemic Stroke A Scientific Statement From the American Heart Association

Stroke is a common and serious disorder, with an incidence of ≈795 000 each year in the United States alone. Worldwide, stroke is a leading cause of death and disability. Recombinant tissue plasminogen activator (rtPA) was approved a decade ago for the treatment of acute ischemic stroke. The guidelines for its use include stroke onset within 3 hours of intravenous drug administration, preceded by a computed tomographic (CT) scan to exclude the presence of hemorrhage, which is a contraindication to the use of the drug. Although randomized, controlled studies in Europe and North America demonstrated the efficacy of this treatment, it also was associated with an incidence of intracranial hemorrhage of 6.4%,1,2⇓ which was shown on subsequent studies to be even greater if there was not strict adherence to the administration protocol.3 The goal of these controlled studies was to evaluate patient outcome. There was no attempt to determine the site, or even the actual presence, of a vascular occlusion, the degree of tissue injury, or the amount of tissue at risk for further injury that might be salvageable. More than a decade later, progress for treating acute ischemic stroke has been slow,4,5⇓ yet the goals for treating this common disease have expanded. First, there is the need to extend the therapeutic window from 3 to ≥6 hours. Even with the rapid communication and transportation in our societies today, very few patients present for treatment within 3 hours.6 Second, there is the desire to improve the efficacy of treatment. It had been shown even before the randomized, controlled studies that intravenous rtPA works better in small peripheral vessels than in the large vessels at the skull base.7 Third, there is a need to decrease the complication rate, especially if patients are to be …

Antidepressant effect on connectivity of the mood-regulating circuit : An fMRI study

The mechanisms by which antidepressant-induced neurochemical changes lead to physiological changes in brain circuitry and ultimately an antidepressant response remain unclear. This study investigated the effects of sertraline, a selective serotonin reuptake inhibitor antidepressant, on corticolimbic connectivity, using functional magnetic resonance imaging (fMRI). In all, 12 unmedicated unipolar depressed patients and 11 closely matched healthy control subjects completed two fMRI scanning sessions at baseline and after 6 weeks. Depressed patients received treatment with sertraline between the two sessions. During each fMRI session, subjects first completed a conventional block-design experiment. Next, connectivity between cortical and limbic regions was measured using correlations of low-frequency blood oxygen level-dependent (BOLD) fluctuations (LFBF) during continuous exposure to neutral, positive, and negative pictures. At baseline, depressed patients had decreased corticolimbic LFBF correlations compared to healthy subjects during the resting state and on exposure to emotionally valenced pictures. At rest and on exposure to neutral and positive pictures, LFBF correlation between the anterior cingulate cortex and limbic regions was significantly increased in patients after treatment. However, on exposure to negative pictures, corticolimbic LFBF correlations remained decreased in depressed patients. The results of this study are consistent with the hypothesis that antidepressant treatment may increase corticolimbic connectivity, thereby possibly increasing the regulatory influence of cortical mood-regulating regions over limbic regions.

Correlations in low-frequency BOLD fluctuations reflect cortico-cortical connections.

Cross-correlation of low-frequency temporal fluctuations (<0.08 Hz) was used to correlate widely separated anatomic regions during continuous performance of a spatial working memory task. The regions of highest correlation to right-hemisphere dorsolateral prefrontal cortex correspond to the regions of largest baseline signal change in a conventional block-style functional MRI paradigm. Additionally, it is shown that the correlations between elements of the functional network increase during performance of a task that activates the network when compared to a task that does not directly stimulate the functionally connected network.

Lesion-induced pseudo-dominance at functional magnetic resonance imaging: implications for preoperative assessments

OBJECTIVE:To illustrate how lesion-induced neurovascular uncoupling at functional magnetic resonance imaging (fMRI) can mimic hemispheric dominance opposite the side of a lesion preoperatively. METHODS:We retrospectively reviewed preoperative fMRI mapping data from 50 patients with focal brain abnormalities to establish patterns of hemispheric dominance of language, speech, visual, or motor system functions. Abnormalities included gliomas (31 patients), arteriovenous malformations (AVMs) (11 patients), other congenital lesions (4 patients), encephalomalacia (3 patients), and tumefactive encephalitis (1 patient). A laterality ratio of fMRI hemispheric dominance was compared with actual hemispheric dominance as verified by electrocortical stimulation, Wada testing, postoperative and posttreatment deficits, and/or lesion-induced deficits. fMRI activation maps were generated with cross-correlation (P < 0.001) or t test (P < 0.001) analysis. RESULTS:In 50 patients, a total of 85 functional areas were within 5 mm of the edge of a potentially resectable lesion. In 23 of these areas (27%), reduced fMRI signal in perilesional eloquent cortex in conjunction with preserved or increased signal in homologous contralateral brain areas revealed functional dominance opposite the side of the lesion. This suggested possible lesion-induced transhemispheric cortical reorganization to homologous brain regions (homotopic reorganization). In seven patients, however, the fMRI data were inconsistent with other methods of functional localization. In two patients with left inferior frontal gyrus gliomas and in one patient with focal tumefactive meningoencephalitis, fMRI incorrectly suggested strong right hemispheric speech dominance. In two patients with lateral precentral gyrus region gliomas and one patient with a left central sulcus AVM, the fMRI pattern incorrectly suggested primary corticobulbar motor dominance contralateral to the side of the lesion. In a patient with a right superior frontal gyrus AVM, fMRI revealed pronounced left dominant supplementary motor area activity in response to a bilateral complex motor task, but right superior frontal gyrus perilesional hemorrhage and edema subsequently caused left upper-extremity plegia. Pathophysiological factors that might have caused neurovascular uncoupling and facilitated pseudo-dominance at fMRI in these patients included direct tumor infiltration, neovascularity, cerebrovascular inflammation, and AVM-induced hemodynamic effects. Sixteen patients had proven (1 patient), probable (2 patients), or possible (13 patients) but unproven lesion-induced homotopic cortical reorganization. CONCLUSION:Lesion-induced neurovascular uncoupling causing reduced fMRI signal in perilesional eloquent cortex, in conjunction with normal or increased activity in homologous brain regions, may simulate hemispheric dominance and lesion-induced homotopic cortical reorganization.

Comparison of rhyming and word generation with FMRI

Functional magnetic resonance imaging (FMRI) has been successfully used to non‐invasively map language function, but has several disadvantages. These include severe motion sensitivity, which limits overt verbal responses in behavioral paradigms, such as word generation. The lack of overt responses prevents behavioral validation, making data interpretation difficult. Our objective was to compare the FMRI activation patterns of a novel silent rhyme determination task requiring a non‐verbal response, to covert word generation from visually presented letters. Five strongly right‐handed subjects performed both tasks during multi‐slice coronal echo‐planar T2*–weighted FMRI. Single subject activation maps were generated for each task by correlation analysis of single pixel time series to a boxcar reference function. These maps for the two tasks were separately interpolated to 2563, transformed into Talairach space, summed, and thresholded at t>6. Combined activation maps from both tasks showed similar robust perisylvian language area activation, including inferior frontal gyrus, posterior superior temporal lobe, and fusiform gyrus. Subjects performed well on the rhyming task, which activated left hemisphere cortical regions more selectively than the word generation task. The rhyming task showed less activation than the word generation task in areas typically not considered specifically related to language function, such as the dorsolateral prefrontal cortex and anterior cingulate. The rhyming task is a useful tool for brain mapping and clinical applications, potentially more specific to cortical language areas than verbal fluency. Hum. Brain Mapping 10:99–106, 2000.

Cytomegalovirus encephalitis in acquired immunodeficiency syndrome (AIDS)

Cytomegalovirus encephalitis (CMVE) is frequently diagnosed only at postmortem because its specific clinical features have not been fully identified. We have described the clinical, radiologic, and laboratory features of CMVE in a retrospective review of 14 autopsy-confirmed cases of CMVE and compared them with a control group of demented acquired immunodeficiency syndrome (AIDS) patients without CMVE. CMVE was more common among homosexual men, and a subacute onset was more typical (mean duration of presenting symptoms was 3.5 weeks versus 18 weeks in demented controls). Median survival times were 4.6 weeks for CMVE and 28 weeks for controls. CMVE was accompanied by prominent systemic CMV infection at autopsy, including CMV adrenalitis (92%), CMV pneumonitis (42%), systemic Mycobacterium avium intracellulare (MAI; 58%), and CMV retinitis (58%). Hyponatremia and MAI bacteremia were found in 58% of CMVE cases. Polymerase chain reaction (PCR) of CSF samples identified CMV genome in 33% of CMVE cases. CMVE was associated with periventricular enhancement on CTs and periventricular lesions with meningeal enhancement on MRI scans. CMVE should be particularly suspected in homosexual men presenting with subacute encephalopathy who have had AIDS for more than 1 year and have a history of systemic CMV infection. Other features supporting the diagnosis of CMVE include periventricular lesions, hyponatremia, and identification of CMV genome in CSF by PCR.

Regional brain atrophy in HIV-1 infection: association with specific neuropsychological test performance

Quantified magnetic resonance imaging (MRI) was related to neuropsychological (NP) test scores in an asymptomatic HIV‐1 seropositive group, a non‐demented AIDS/ARC group, a group of subjects with HIV‐1 dementia, and a seronegative control group. The MRIs were quantified using three planimetric measures of brain structure: the bicaudate ratio (a measure of caudate region atrophy), the bifrontal ratio (a measure of frontal region atrophy), and the ventricle to brain ratio (a measure of overall cerebral atrophy). Cognitive performance was assessed with standard NP tests. Significant correlations between the MRI ratios and many of the NP tests were observed. Of the tests grooved pegboard, part B of the trail making test, the verbal fluency test, and the digit span forward were associated with MRI abnormalities. The bicaudate ratio was most closely associated with the NP tests. These findings indicate that ventricular enlargement, especially in the region of the caudate, is closely related to poor NP test performance in HIV‐1 infection.

Media violence exposure and frontal lobe activation measured by functional magnetic resonance imaging in aggressive and nonaggressive adolescents.

Objective: To understand better the relation between media violence exposure, brain functioning, and trait aggression, this study investigated the association between media violence exposure and brain activation as measured by functional magnetic resonance imaging (fMRI) in groups of normal adolescents and adolescents with disruptive behavior disorder (DBD) with aggressive features. Methods: Seventy-one participants underwent neuropsychologic evaluation and assessment of exposure to violent media. Subjects also were evaluated with fMRI while performing a counting Stroop (CS) task. Results: Frontal lobe activation was reduced in aggressive subjects compared with control subjects. In addition, differences in frontal lobe activation were associated with differences in media violence exposure. Specifically, activation during performance of the CS in control subjects with high media violence exposure resembled that seen in DBD subjects. Conclusions: Our findings suggest that media violence exposure may be associated with alterations in brain functioning whether or not trait aggression is present.

Comparison of fMRI and intraoperative direct cortical stimulation in localization of receptive language areas

PURPOSE The purpose of this work was to compare the cortical localization of receptive speech using functional MRI (fMRI) and direct intraoperative electrical stimulation. METHOD Three strongly right-handed patients with primary neoplasms of the left parasylvian region underwent fMRI while subjected to a passive listening task designed to activate receptive language areas. All three subjects then underwent awake intraoperative language mapping using direct electrical stimulation of the cortex. RESULTS In all three subjects, similar, but nonidentical, cortical regions were identified as involved in receptive language function by fMRI and direct cortical stimulation mapping. CONCLUSION fMRI provides excellent receptive language mapping, but its results must be interpreted with caution due to conceptual and technical differences from direct cortical stimulation mapping.