Andrew J. Kalnin

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.

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.

Cerebral activation patterns during working memory performance in multiple sclerosis using FMRI.

Working memory deficits are common in Multiple Sclerosis (MS) and have been identified behaviorally in numerous studies. Despite recent advance in functional magnetic resonance imaging (fMRI), few published studies have examined cerebral activations associated with working memory dysfunction in MS. The present study examines brain activation patterns during performance of a working memory task in individuals with clinically definite MS, compared to healthy controls (HC). fMRI was performed using a 1.5 Tesla GE scanner during a modified Paced Auditory Serial Addition Test (mPASAT). Participants were 6 individuals with MS with working memory impairment as evidenced on neuropsychological testing, 5 individuals with MS without working memory impairment, and 5 HC. Groups were demographically equivalent. Data were analyzed using Statistical Parametric Mapping (SPM99) software, with a stringent significance level (alpha < .005, voxel extent ≥ 8). Both MS groups and the HC group were able to perform the task, with comparable performance in terms of numbers of correct responses. Activation patterns within the HC and MS not-impaired groups were noted in similar brain regions, consistent with published observations in healthy samples. That is, activations were lateralized to the left hemisphere, involving predominantly frontal regions. In contrast, the MS impaired group showed greater right frontal and right parietal lobe activation, when compared with the HC group. Thus, it appears that working memory dysfunction in MS is associated with altered patterns of cerebral activation that are related to the presence of cognitive impairment, and not solely a function of MS. This research was supported by the Henry H. Kessler Foundation, the Hyde and Watson Foundation and the Kirby Foundation. The authors wish to thank Rinki Jajoo for her help with data management, as well as Dr. Scott Millis and Dr. Dane Cook for their statistical advice. Dr. Christopher Christodoulou is now in the Department of Neurology, State University of New York at Stony Brook. Dr. Joseph Ricker is now in the Department of Physical Medicine and Rehabilitation, University of Pittsburgh.

fMRI study of acupuncture-induced periaqueductal gray activity in humans

BOLD fMRI was used to study acupuncture-induced activation (increase in the BOLD signal from undetectable) of the periaqueductal gray (PAG) and two somatosensory cortical areas in seven healthy human subjects. Mechanical stimulation (push-pull) was given to the LI4 (Hoku) acupoint or to a non-acupoint. The stimulation paradigm consisted of 5 runs, each consisting of four 30 s On/30 s OFF periods over 30 min. The scan for each ON period was analyzed individually. The PAG and cortical areas showed different activity patterns. PAG activity was episodic and reliably demonstrated after 20–25 min of stimulation; both cortical areas, however, were active >90% of the time. Stimulation of a non-acupoint (leg) resulted in reduced levels of PAG and cortical activity.

Intraoperative functional MRI using a real-time neurosurgical navigation system.

A 42-year-old-man had focal left hand motor seizures. MR studies demonstrated a right posterior frontal brain tumor. Functional MRI was performed, localizing the motor cortex posterior to the lesion. The functional images were integrated with a neurosurgical navigation computer. A real-time intraoperative display of the anatomic and functional images was produced, registered to a neurosurgical probe. Excellent correlation was demonstrated between the functional maps and invasive electrophysiologic mapping performed at the time of craniotomy.

An Investigation of Working Memory Rehearsal in Multiple Sclerosis Using fMRI

The present study examined patterns of cerebral activation during a working memory (WM) rehearsal task in individuals diagnosed with multiple sclerosis (MS) and in healthy adults. BOLD functional magnetic resonance imaging (fMRI)was performed using a 1.5TGE scanner to assess activation during aWMtask adapted fromthe Sternberg paradigm (Sternberg, 1969). Participants included 8 individuals diagnosed with MS, and 5 healthy controls (HCs) matched for age and education. Task difficulty was manipulated by increasing the length of time that strings of letters were to be rehearsed. Findings revealed increased right prefrontal cortex activation and increased right temporal lobe activation in individuals diagnosed with MS compared to HCs. The potential explanations for increased right hemisphere activation in persons with MS are discussed.

Short-Term Violent Video Game Play by Adolescents Alters Prefrontal Activity During Cognitive Inhibition

Prior research has indicated an association between exposure to violent media and aggressive thoughts, feelings, and behavior, potentially as a result of effects on inhibitory mechanisms. However, the role of violence in video games in modulating subsequent neural activity related to cognitive inhibition has received little attention. To examine short-term effects of playing a violent video game, 45 adolescents were randomly assigned to play either a violent or a nonviolent video game for 30 minutes immediately prior to functional magnetic resonance imaging (fMRI). During the fMRI procedure, participants performed a go/no-go task that required them to press a button for each target stimulus and withhold the response for non-target stimuli. Participants who played the violent game demonstrated a lower BOLD response in right dorsolateral prefrontal cortex (DLPFC) when responses were appropriately inhibited. The DLPFC is involved with executive functioning, including suppression of unwanted thoughts and behaviors. In addition, responses in the DLPFC demonstrated stronger inverse connectivity with precuneus in the nonviolent game players. These results provide evidence that playing a violent video game can modulate prefrontal activity during cognitive inhibition.

BOLD fMRI activation induced by vagus nerve stimulation in seizure patients

Objective: To identify the cerebral activated regions associated with the vagus nerve stimulation in epilepsy patients. Design: Blood oxygenation level dependent functional magnetic resonance imaging (BOLD fMRI) was employed to detect areas of the brain activated by vagus nerve stimulation in five patients with documented complex partial seizures. Methods: Functional MRI was done on a GE 1.5T Echospeed horizon scanner. Before each patient entered the scanner, the vagal nerve stimulator was set to a specific ON–OFF paradigm so that the data could be analysed using a box-car type of design. The brains were scanned both anatomically and functionally. The functional images were corrected for head motion and co-registered to the anatomical images. Maps of the activated areas were generated and analysed using the brain mapping software, SPM99. The threshold for activation was chosen as p < 0.001. Results: All patients showed activation in the frontal and occipital lobes. However, activation in the thalamus was seen only in the two patients with improved seizure control. Conclusions: BOLD fMRI can detect activation associated with vagus nerve stimulation. There may be a relation between thalamic activation and a favourable clinical outcome.

Executive functioning characteristics associated with ADHD comorbidity in adolescents with disruptive behavior disorders

The nature of executive dysfunction in youth with disruptive behavior disorders (DBD) remains unclear, despite extensive research in samples of children with attention-deficit hyperactivity disorder (ADHD). To determine the relationship between DBD, ADHD, and executive function deficits in aggressive teens, adolescents with DBD and comorbid ADHD (DBD + ADHD; n = 25), DBD without ADHD (DBD-ADHD; n = 23), and healthy controls (HC; n = 25) were compared on neurocognitive tests and questionnaires measuring executive functioning. Teens with DBD + ADHD performed worse on both neurocognitive and questionnaire measures of executive function than the DBD-ADHD and HC groups. Results suggest that subgroups of DBD may exist depending on the presence or absence of comorbid ADHD, which may have implications for the selection and efficacy of treatment strategies.

ASFNR Recommendations for Clinical Performance of MR Dynamic Susceptibility Contrast Perfusion Imaging of the Brain

This article discusses the utility of DSC perfusion MR imaging in the setting of tumors and ischemia and suggests guidance on its implementation, processing, interpretation, and reporting. SUMMARY: MR perfusion imaging is becoming an increasingly common means of evaluating a variety of cerebral pathologies, including tumors and ischemia. In particular, there has been great interest in the use of MR perfusion imaging for both assessing brain tumor grade and for monitoring for tumor recurrence in previously treated patients. Of the various techniques devised for evaluating cerebral perfusion imaging, the dynamic susceptibility contrast method has been employed most widely among clinical MR imaging practitioners. However, when implementing DSC MR perfusion imaging in a contemporary radiology practice, a neuroradiologist is confronted with a large number of decisions. These include choices surrounding appropriate patient selection, scan-acquisition parameters, data-postprocessing methods, image interpretation, and reporting. Throughout the imaging literature, there is conflicting advice on these issues. In an effort to provide guidance to neuroradiologists struggling to implement DSC perfusion imaging in their MR imaging practice, the Clinical Practice Committee of the American Society of Functional Neuroradiology has provided the following recommendations. This guidance is based on review of the literature coupled with the practice experience of the authors. While the ASFNR acknowledges that alternate means of carrying out DSC perfusion imaging may yield clinically acceptable results, the following recommendations should provide a framework for achieving routine success in this complicated-but-rewarding aspect of neuroradiology MR imaging practice.