Nasim Maleki

Alterations in brain structure and functional connectivity in prescription opioid-dependent patients.

A dramatic increase in the use and dependence of prescription opioids has occurred within the last 10 years. The consequences of long-term prescription opioid use and dependence on the brain are largely unknown, and any speculation is inferred from heroin and methadone studies. Thus, no data have directly demonstrated the effects of prescription opioid use on brain structure and function in humans. To pursue this issue, we used structural magnetic resonance imaging, diffusion tensor imaging and resting-state functional magnetic resonance imaging in a highly enriched group of prescription opioid-dependent patients [(n=10); from a larger study on prescription opioid dependent patients (n=133)] and matched healthy individuals (n=10) to characterize possible brain alterations that may be caused by long-term prescription opioid use. Criteria for patient selection included: (i) no dependence on alcohol or other drugs; (ii) no comorbid psychiatric or neurological disease; and (iii) no medical conditions, including pain. In comparison to control subjects, individuals with opioid dependence displayed bilateral volumetric loss in the amygdala. Prescription opioid-dependent subjects had significantly decreased anisotropy in axonal pathways specific to the amygdala (i.e. stria terminalis, ventral amygdalofugal pathway and uncinate fasciculus) as well as the internal and external capsules. In the patient group, significant decreases in functional connectivity were observed for seed regions that included the anterior insula, nucleus accumbens and amygdala subdivisions. Correlation analyses revealed that longer duration of prescription opioid exposure was associated with greater changes in functional connectivity. Finally, changes in amygdala functional connectivity were observed to have a significant dependence on amygdala volume and white matter anisotropy of efferent and afferent pathways of the amygdala. These findings suggest that prescription opioid dependence is associated with structural and functional changes in brain regions implicated in the regulation of affect and impulse control, as well as in reward and motivational functions. These results may have important clinical implications for uncovering the effects of long-term prescription opioid use on brain structure and function.

Painful Heat Reveals Hyperexcitability of the Temporal Pole in Interictal and Ictal Migraine States

During migraine attacks, alterations in sensation accompanying headache may manifest as allodynia and enhanced sensitivity to light, sound, and odors. Our objective was to identify physiological changes in cortical regions in migraine patients using painful heat and functional magnetic resonance imaging (fMRI) and the structural basis for such changes using diffusion tensor imaging (DTI). In 11 interictal patients, painful heat threshold + 1°C was applied unilaterally to the forehead during fMRI scanning. Significantly greater activation was identified in the medial temporal lobe in patients relative to healthy subjects, specifically in the anterior temporal pole (TP). In patients, TP showed significantly increased functional connectivity in several brain regions relative to controls, suggesting that TP hyperexcitability may contribute to functional abnormalities in migraine. In 9 healthy subjects, DTI identified white matter connectivity between TP and pulvinar nucleus, which has been related to migraine. In 8 patients, fMRI activation in TP with painful heat was exacerbated during migraine, suggesting that repeated migraines may sensitize TP. This article investigates a nonclassical role of TP in migraineurs. Observed temporal lobe abnormalities may provide a basis for many of the perceptual changes in migraineurs and may serve as a potential interictal biomarker for drug efficacy.

Concurrent functional and structural cortical alterations in migraine.

Aim: Various animal and human studies have contributed to the idea of cortical structural–functional alterations in migraine. Defining concurrent cortical alterations may provide specific insights into the unfolding adaptive or maladaptive changes taking place in cortex in migraine. Methods: From a group of 60 episodic migraineurs, 20 were recruited to the study. Using high-resolution magnetic resonance imaging, structural and functional cortical measures were compared in migraineurs who experienced increased frequency of attacks (HF; 8–14 days/month; n = 10), to those who experienced less frequent migraine attacks (LF; < 2 days/month; n = 10), and to healthy controls (HC; n = 20). Results: Parallel structural and functional differences were found as follows: (i) HF patients showed higher thickness in the area representing the face in the post-central gyrus, which correlated with the observed stronger functional activation, suggesting adaptation to repeated sensory drive; (ii) smaller cortical volume was observed in the cingulate cortex that correlated with lower activation in the HF group; and (iii) similarly significant structural and functional differences (HF > LF) were observed in the insula that may reflect potential alteration in affective processing. Conclusion: These results suggest differential response patterns in the sensory vs. affective processing regions in the brain that may be an adaptive response to repeated migraine attacks.

Migraine attacks the Basal Ganglia

BackgroundWith time, episodes of migraine headache afflict patients with increased frequency, longer duration and more intense pain. While episodic migraine may be defined as 1-14 attacks per month, there are no clear-cut phases defined, and those patients with low frequency may progress to high frequency episodic migraine and the latter may progress into chronic daily headache (> 15 attacks per month). The pathophysiology of this progression is completely unknown. Attempting to unravel this phenomenon, we used high field (human) brain imaging to compare functional responses, functional connectivity and brain morphology in patients whose migraine episodes did not progress (LF) to a matched (gender, age, age of onset and type of medication) group of patients whose migraine episodes progressed (HF).ResultsIn comparison to LF patients, responses to pain in HF patients were significantly lower in the caudate, putamen and pallidum. Paradoxically, associated with these lower responses in HF patients, gray matter volume of the right and left caudate nuclei were significantly larger than in the LF patients. Functional connectivity analysis revealed additional differences between the two groups in regard to response to pain.ConclusionsSupported by current understanding of basal ganglia role in pain processing, the findings suggest a significant role of the basal ganglia in the pathophysiology of the episodic migraine.

The Young Brain and Concussion: Imaging as a Biomarker for Diagnosis and Prognosis

Concussion (mild traumatic brain injury (mTBI)) is a significant pediatric public health concern. Despite increased awareness, a comprehensive understanding of the acute and chronic effects of concussion on central nervous system structure and function remains incomplete. Here we review the definition, epidemiology, and sequelae of concussion within the developing brain, during childhood and adolescence, with current data derived from studies of pathophysiology and neuroimaging. These findings may contribute to a better understanding of the neurological consequences of traumatic brain injuries, which in turn, may lead to the development of brain biomarkers to improve identification, management and prognosis of pediatric patients suffering from concussion.

Mapping pain activation and connectivity of the human habenula.

The habenula, located in the posterior thalamus, is implicated in a wide array of functions. Animal anatomical studies have indicated that the structure receives inputs from a number of brain regions (e.g., frontal areas, hypothalamic, basal ganglia) and sends efferent connections predominantly to the brain stem (e.g., periaqueductal gray, raphe, interpeduncular nucleus). The role of the habenula in pain and its anatomical connectivity are well-documented in animals but not in humans. In this study, for the first time, we show how high-field magnetic resonance imaging can be used to detect habenula activation to noxious heat. Functional maps revealed significant, localized, and bilateral habenula responses. During pain processing, functional connectivity analysis demonstrated significant functional correlations between the habenula and the periaqueductal gray and putamen. Probabilistic tractography was used to assess connectivity of afferent (e.g., putamen) and efferent (e.g., periaqueductal gray) pathways previously reported in animals. We believe that this study is the first report of habenula activation by experimental pain in humans. Since the habenula connects forebrain structures with brain stem structures, we suggest that the findings have important implications for understanding sensory and emotional processing in the brain during both acute and chronic pain.

Direct optic nerve pulvinar connections defined by diffusion MR tractography in humans: Implications for photophobia

The pathway that underlies exacerbation of migraine headache by light has not been elucidated in the human brain but has recently been reported in a rodent model. We employ diffusion weighted imaging and probabilistic tractography to map connectivity of direct pathways from the optic nerve to the pulvinar implicated with whole‐body allodynia during migraine. Nine healthy subjects were recruited to the study and underwent scanning on a 3T magnet. We were able to define well‐known image‐forming (optic nerve ‐> lateral geniculate ‐> visual cortex) as well as a less known nonimage forming visual pathway from the optic chiasm to the pulvinar, and from the pulvinar to several associative cortical brain regions. Such pathway may allow photic signals to converge on a thalamic region we described recently to be selectively activated during migraine headache. Consistent with physiological and anatomical studies in rats, the data provide an anatomical substrate for exacerbation of migraine headache by light in the human. Hum Brain Mapp, 2012.

Optimization of background suppression for arterial spin labeling perfusion imaging

ObjectTo present an algorithm for optimization of background suppression pulse timing for arterial spin labeling (ASL) perfusion imaging.Materials and methodsAn algorithm for optimization of background suppression pulse timing is proposed. Numerical optimization of timing of the background suppression pulses is investigated in both constrained and unconstrained ASL sequences. The performance of the parameters from the algorithm is evaluated in phantom and also in vivo in five human subjects.ResultsThe background signal is suppressed to less than 1% across a broad range of T1s with a modest number of inversion pulses using the timings acquired from the numerical optimization algorithm proposed in this study. The performance of the parameters from the algorithm is also confirmed in vivo.ConclusionSuccessful background suppression over a broad range of tissues is achievable. Values for optimal pulse timing in both pulsed and continuous ASL studies are reported to facilitate sequence design with different labeling parameters.

Migraine: Maladaptive Brain Responses to Stress

Migraine offers a unique model to understand the consequences of repeated stressors on the brain. Repeated stressors can alter the normal response of physiological systems, and this concept has been termed “allostatic load.” In the case of the brain, the effects of repeated stress may lead to alteration in brain networks both functionally and structurally. As a result, the brain responds abnormally to environmental conditions (psychological or physiological). Here, we present an alternative perspective on migraine disease and propose that changes in brain states may occur as a result of repeated migraine attacks through maladaptive coping mechanisms. The cascade of these effects can lead to further deterioration of adaptation and thus lead to transformation or chronification of the disease.

Blood flow quantification of the human retina with MRI.

The purpose of this study was to investigate the feasibility of measuring blood flow to the retina using arterial spin labeling MRI, a quantitative, noninvasive tomographic technique. Blood flow imaging was performed in a single axial slice through both eyes of five healthy volunteers with no history of retinal diseases. The imaging was optimized to minimize the errors from motion and nonuniform magnetic fields caused by proximity to the sinuses. Key hemodynamic factors for flow quantification, including arterial transit delay and the apparent decay time of the signal, were estimated by repeated measurements with different arterial spin labeling timing. A clearly elevated signal, consistent with the anatomical location of the retina, was observed in all subjects. The measured blood flow to a 1 cm × 1.47 cm section of the retina, centered on the fovea, was 1.75 ± 0.54 µL/mm2/min (total blood flow of 261 ± 87 µL/min). The arterial transit delay from a labeling plane 5 cm below the slice was 1137 ± 288 ms. These results establish the feasibility of measuring blood flow to the retina with MRI, and support the future characterization of the healthy and diseased ocular circulation with this method. Copyright