Separating function from structure in perfusion imaging of the aging brain

The accuracy of cerebral blood flow (CBF) imaging in humans has been impeded by the partial volume effects (PVE), which are a consequence of the limited spatial resolution. Because of brain atrophy, PVE can be particularly problematic in imaging the elderly and can considerably overestimate the CBF difference with the young. The primary goal of this study was to separate the structural decline from the true CBF reduction in elderly. To this end, a PVE‐correction algorithm was applied on the CBF images acquired with spin‐echo EPI continuous arterial spin labeling MRI (voxel size = 3.4 × 3.4 × 8 mm³). Tissue‐specific CBF images that were independent of voxels' tissue fractional volume were obtained in elderly (N = 30) and young (N = 26); mean age difference was 43 years. Globally, PVE‐corrected gray matter CBF was 88.2 ± 16.1 and 107.3 ± 17.5 mL/100 g min^?1 in elderly and young, respectively. The largest PVE contribution was found in the frontal lobe and accounted for an additional 10% and 12% increase in the age‐related CBF difference between men and women, respectively. The GM‐to‐WM CBF ratios were found to be on average 3.5 in elderly and 3.9 in young. Whole brain voxelwise comparisons showed marked CBF decrease in anterior cingulate (bilateral), caudate (bilateral), cingulate gyrus (bilateral), cuneus (left), inferior frontal gyrus (left), insula (left), middle frontal gyrus (left), precuneus (bilateral), prefrontal cortex (bilateral), and superior frontal gyrus (bilateral) in men and amygdala (bilateral), hypothalamus (left), hippocampus (bilateral), and middle frontal gyrus (right) in women. Hum Brain Mapp 2009. © 2009 Wiley‐Liss, Inc.     

A double dissociation of ventromedial prefrontal cortical responses to sad and happy stimuli in depressed and healthy individuals.

BACKGROUND: The ventromedial prefrontal cortex (VMPFC) is a region implicated in the assessment of the rewarding potential of stimuli and may be dysfunctional in major depressive disorder (MDD). The few studies examining prefrontal cortical responses to emotive stimuli in MDD have indicated increased VMPFC responses to pleasant images but decreased responses to sad mood provocation when compared with healthy individuals. We wished to corroborate these results by examining neural responses to personally relevant happy and sad stimuli in MDD and healthy individuals within the same paradigm. METHODS: Neural responses to happy and sad emotional stimuli (autobiographical memory prompts and congruent facial expressions) were measured using blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) in MDD (n = 12) and healthy (n = 12) individuals. RESULTS: Increased and decreased responses in VMPFC were observed in MDD and healthy individuals, respectively, to happy stimuli, whereas the pattern was reversed for MDD and healthy individual responses to sad stimuli. These findings were not explained by medication effects in depressed individuals. CONCLUSIONS: These findings indicate a double dissociation of the pattern of VMPFC response to happy and sad stimuli in depressed and healthy individuals and suggest abnormal reward processing in MDD.     

Gender difference in neural response to psychological stress

Gender is an important biological determinant of vulnerability to psychosocial stress. We used perfusion based functional magnetic resonance imaging (fMRI) to measure cerebral blood flow (CBF) responses to mild to moderate stress in 32 healthy people (16 males and 16 females). Psychological stress was elicited using mental arithmetic tasks under varying pressure. Stress in men was associated with CBF increase in the right prefrontal cortex (RPFC) and CBF reduction in the left orbitofrontal cortex (LOrF), a robust response that persisted beyond the stress task period. In contrast, stress in women primarily activated the limbic system, including the ventral striatum, putamen, insula and cingulate cortex. The asymmetric prefrontal activity in males was associated with a physiological index of stress responses-salivary cortisol, whereas the female limbic activation showed a lower degree of correlations with cortisol. Conjunction analyses indicated only a small degree of overlap between the stress networks in men and women at the threshold level of P < 0.01. Increased overlap of stress networks between the two genders was revealed when the threshold for conjunction analyses was relaxed to P < 0.05. Further, machine classification was used to differentiate the central stress responses between the two genders with over 94% accuracy. Our study may represent an initial step in uncovering the neurobiological basis underlying the contrasting health consequences of psychosocial stress in men and women.     

Amygdala and orbitofrontal reactivity to social threat in individuals with impulsive aggression.

BACKGROUND: Converging evidence from animal and human lesion studies implicates the amygdala and orbitofrontal cortex (OFC) in emotional regulation and aggressive behavior. However, it remains unknown if functional deficits exist in these specific brain regions in clinical populations in which the cardinal symptom is impulsive aggression. We have previously shown that subjects diagnosed with intermittent explosive disorder (IED), a psychiatric disorder characterized by reactive aggressive behavior, perform poorly on facial emotion recognition tasks. In this study we employed a social-emotional probe of amygdala-OFC function in individuals with impulsive aggression. METHODS: Ten unmedicated subjects with IED and 10 healthy, matched comparison subjects (HC) underwent functional magnetic resonance imaging while viewing blocks of emotionally salient faces. We compared amygdala and OFC reactivity to faces between IED and HC subjects, and examined the relationship between the extent of activation in these regions and extent of prior history of aggressive behavior. RESULTS: Relative to controls, individuals with IED exhibited exaggerated amygdala reactivity and diminished OFC activation to faces expressing anger. Extent of amygdala and OFC activation to angry faces were differentially related to prior aggressive behavior across subjects. Unlike controls, aggressive subjects failed to demonstrate amygdala-OFC coupling during responses to angry faces. CONCLUSIONS: These findings provide evidence of amygdala-OFC dysfunction in response to an ecologically-valid social threat signal (processing angry faces) in individuals with a history of impulsive aggressive behavior, and further substantiate a link between a dysfunctional cortico-limbic network and aggression.     

Enhanced affective brain representations of chocolate in cravers vs. non-cravers

To examine the neural circuitry involved in food craving, in making food particularly appetitive and thus in driving wanting and eating, we used fMRI to measure the response to the flavour of chocolate, the sight of chocolate and their combination in cravers vs. non-cravers. Statistical parametric mapping (SPM) analyses showed that the sight of chocolate produced more activation in chocolate cravers than non-cravers in the medial orbitofrontal cortex and ventral striatum. For cravers vs. non-cravers, a combination of a picture of chocolate with chocolate in the mouth produced a greater effect than the sum of the components (i.e. supralinearity) in the medial orbitofrontal cortex and pregenual cingulate cortex. Furthermore, the pleasantness ratings of the chocolate and chocolate-related stimuli had higher positive correlations with the fMRI blood oxygenation level-dependent signals in the pregenual cingulate cortex and medial orbitofrontal cortex in the cravers than in the non-cravers. To our knowledge, this is the first study to show that there are differences between cravers and non-cravers in their responses to the sensory components of a craved food in the orbitofrontal cortex, ventral striatum and pregenual cingulate cortex, and that in some of these regions the differences are related to the subjective pleasantness of the craved foods. Understanding individual differences in brain responses to very pleasant foods helps in the understanding of the mechanisms that drive the liking for specific foods and thus intake of those foods.     

Changes in regional brain activity in major depression after successful treatment with antidepressant drugs

Relative regional cerebral blood flow was measured with single photon emission computed tomography (SPECT) using ^99mTc-hexamethyl-propyleneamine oxime (^99mTc-HMPAO) in 16 patients with major depression while they were in the depressed state as well as in remission. All patients were closely matched with regard to medication status. In the depressed state, significant reductions in tracer uptake were found in the left superior frontal, bilateral parietal and right lateral temporal cortex. During remission, significant increases in uptake were found in the left superior frontal, right parietal and right lateral temporal cortex. There were no significant differences in tracer uptake between patients in remission and controls. These findings suggest that the regional decreases in tracer uptake observed in the depressed state might be a state-related abnormality.     

Genetic variation in G72 correlates with brain activation in the right middle temporal gyrus in a verbal fluency task in healthy individuals

The D ‐amino acid oxidase activator gene (G72) has been found associated with several psychiatric disorders such as schizophrenia, major depression, and bipolar disorder. Impaired performance in verbal fluency tasks is an often replicated finding in the mentioned disorders. In functional neuroimaging studies, this dysfunction has been linked to signal changes in prefrontal and lateral temporal areas and could possibly constitute an endophenotype. Therefore, it is of interest whether genes associated with the disorders, such as G72, modulate verbal fluency performance and its neural correlates. Ninety‐six healthy individuals performed a semantic verbal fluency task while brain activation was measured with functional MRI. All subjects were genotyped for two single nucleotide polymorphisms (SNP) in the G72 gene, M23 (rs3918342) and M24 (rs1421292), that have previously shown association with the above‐mentioned disorders. The effect of genotype on brain activation was assessed with fMRI during a semantic verbal fluency task. Although there were no differences in performance, brain activation in the right middle temporal gyrus (BA 39 ) and the right precuneus (BA 7) was positively correlated with the number of M24 risk alleles in the G72 gene. G72 genotype does modulate brain activation during language production on a semantic level in key language areas. These findings are in line with structural and functional imaging studies in schizophrenia, which showed alterations in the right middle temporal gyrus. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.     

Epigenetic variation in the serotonin transporter gene predicts resting state functional connectivity strength within the salience‐network

Genetic variation in the serotonin transporter gene (SLC6A4) has been associated with psychopathology and aberrant brain functioning in a plethora of clinical and imaging studies. In contrast, the neurobiological correlates of epigenetic signatures in SLC6A4, such as DNA methylation profiles, have only recently been explored in human brain imaging research. The present study is the first to apply a resting state functional magnetic resonance imaging approach to identify changes in brain networks related to SLC6A4 promoter methylation (N = 74 healthy individuals). The amygdalae were defined as seed regions given that resting state functional connectivity in this brain area is under serotonergic control and relates to a broad range of psychiatric phenotypes. We further used bisulfite pyrosequencing to analyze quantitative methylation at 83 CpG sites within a promoter‐associated CpG island of SLC6A4 from blood‐derived DNA samples. The major finding of this study indicates a positive relation of SLC6A4 promoter methylation and amygdaloid resting state functional coupling with key nodes of the salience network (SN) including the anterior insulae and the dorsal anterior cingulate cortices. Increased intra‐network connectivity in the SN is thought to facilitate the detection and subsequent processing of potentially negative stimuli and reflects a core feature of psychopathology. As such, epigenetic changes within the SLC6A4 gene predict connectivity patterns in clinically and behaviorally relevant brain networks which may in turn convey increased disease susceptibility. Hum Brain Mapp 36:4361–4371, 2015. © 2015 Wiley Periodicals, Inc.     

Regional cerebral blood flow during cortical spreading depression in rat brain: increased reactive hyperperfusion in low-flow states

The purpose of the present study was to characterize the initial vascular events accompanying cortical spreading depression (CSD) of the rat brain. Regional cerebral blood flow (rCBF) was measured during the first 1–2 min of CSD using ¹⁴C-iodoantipyrine autoradiography. The material included a reference group, and 4 groups where rCBF was altered by indomethacin treatment, hypo- or hypercapnia, or one previous episode of CSD. rCBF did not change prior to, or during the onset of CSD. Thirty seconds later, rCBF increased depending on the pre-existing level of blood flow, i.e. the rise of rCBF was pronounced at depressed flow levels, but small or absent at normal or high flow levels. The prevalent view that CSD is intimately associated with vasodilatation was accordingly not supported. The activated rCBF in normocapnic rats ranged between 93 and 175 ml/100g/min, supra normal values were the exception rather than the rule. The rCBF rise, when present, probably succeeds a period of brain hypoxia, and should be classified as a reactive hyperfusion. The results together with earlier clinical and experimental findings, support that CSD may serve as experimental migraine model.     

Associations between polygenic risk for schizophrenia and brain function during probabilistic learning in healthy individuals

A substantial proportion of schizophrenia liability can be explained by additive genetic factors. Risk profile scores (RPS) directly index risk using a summated total of common risk variants weighted by their effect. Previous studies suggest that schizophrenia RPS predict alterations to neural networks that support working memory and verbal fluency. In this study, we apply schizophrenia RPS to fMRI data to elucidate the effects of polygenic risk on functional brain networks during a probabilistic‐learning neuroimaging paradigm. The neural networks recruited during this paradigm have previously been shown to be altered to unmedicated schizophrenia patients and relatives of schizophrenia patients, which may reflect genetic susceptibility. We created schizophrenia RPS using summary data from the Psychiatric Genetic Consortium (Schizophrenia Working Group) for 83 healthy individuals and explore associations between schizophrenia RPS and blood oxygen level dependency (BOLD) during periods of choice behavior (switch–stay) and reflection upon choice outcome (reward–punishment). We show that schizophrenia RPS is associated with alterations in the frontal pole (P_{WHOLE‐BRAIN‐CORRECTED} = 0.048) and the ventral striatum (P_{ROI‐CORRECTED} = 0.036), during choice behavior, but not choice outcome. We suggest that the common risk variants that increase susceptibility to schizophrenia can be associated with alterations in the neural circuitry that support the processing of changing reward contingencies. Hum Brain Mapp 37:491–500, 2016. © 2015 Wiley Periodicals, Inc.     

脑CT灌注成像在早期重型颅脑损伤患者中的应用

目的探讨脑CT灌注成像在早期重型颅脑损伤患者中的应用。方法收集该院外伤致重型颅脑损伤患者106例(观察组)以及同期轻型脑外伤60例(对照组),均于伤后24 h内进行头颅256排CT灌注成像检查,并比较两组的脑血流灌注率(CBF)、脑血容量(CBV)和平均通过时间(MTT)及3个月后的预后情况等。结果观察组伤后24 h内脑基底节区、脑干、额叶、顶叶CBF低于对照组,MTT高于对照组,差异均有统计学意义(P0.05)。基底节、脑干区、额叶、顶叶区CBF与格拉斯哥预后量表(GOS)评分呈正相关(rs=0.902,rs=0.891,rs=0.859,rs=0.786)。基底节丘脑区CBV与GOS评分有关。结论重型颅脑损伤患者早期的CBF值下降,MTT值延长,且CBF值与预后呈正相关,全脑CT灌注成像对早期判断重型颅脑损伤预后有一定临床应用价值。[国际神经病学神经外科学杂志, 2021, 48(2):149-153]     

Genetic variation in the schizophrenia‐risk gene neuregulin 1 correlates with brain activation and impaired speech production in a verbal fluency task in healthy individuals

Impaired performance in verbal fluency tasks is an often replicated finding in schizophrenia. In functional neuroimaging studies, this dysfunction has been linked to signal changes in prefrontal and temporal areas. Since schizophrenia has a high heritability, it is of interest whether susceptibility genes for the disorder, such as NRG1, modulate verbal fluency performance and its neural correlates. Four hundred twenty‐nine healthy individuals performed a semantic and a lexical verbal fluency task. A subsample of 85 subjects performed an overt semantic verbal fluency task while brain activation was measured with functional magnetic resonance imaging (MRI). NRG1 (SNP8NRG221533; rs35753505) status was determined and correlated with verbal fluency performance and brain activation. For the behavioral measure, there was a linear effect of NRG1 status on semantic but not on lexical verbal fluency. Performance decreased with number of risk‐alleles. In the fMRI experiment, decreased activation in the left inferior frontal and the right middle temporal gyri as well as the anterior cingulate gyrus was correlated with the number of risk‐alleles in the semantic verbal fluency task. NRG1 genotype does influence language production on a semantic level in conjunction with the underlying neural systems. These findings are in line with results of studies in schizophrenia and may explain some of the cognitive and brain activation variation found in the disorder. More generally, NRG1 might be one of several genes that influence semantic language capacities. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.     

精神分裂症患者脑供血情况与认知功能的研究

目的：探讨精神分裂症患者脑供血情况与认知功能之间的关系。方法：对精神分裂症患者100例进行听觉事件相关诱发电位（P300）检查，以评价其认知功能；对认知功能检查“差”和“极差”的患者进行经颅多普勒脑血流图（TCD）检查记录血流峰值及脉动指数，以了解其脑供血情况。结果：100例精神分裂症患者P300检查中有83例认知功能为“差”到“极差”，这83例患者TCD检查结果显示，大脑中动脉和大脑前动脉脉动指数均显著高于我国正常成人常模。结论：精神分裂症患者认知功能普遍较差，可能与其大脑中动脉、大脑前动脉血管舒缩调节功能下降导致大脑前额叶供血不足有关。     

Cerebral perfusion is associated with blast exposure in military personnel without moderate or severe TBI

Due to the use of improvised explosive devices, blast exposure and mild traumatic brain injury (mTBI) have become hallmark injuries of the Iraq and Afghanistan wars. Although the mechanisms of the effects of blast on human neurobiology remain active areas of investigation, research suggests that the cerebrovasculature may be particularly vulnerable to blast via molecular processes that impact cerebral blood flow. Given that recent work suggests that blast exposure, even without a subsequent TBI, may have negative consequences on brain structure and function, the current study sought to further understand the effects of blast exposure on perfusion. One hundred and eighty military personnel underwent pseudo-continuous arterial spin labeling (pCASL) imaging and completed diagnostic and clinical interviews. Whole-brain analyses revealed that with an increasing number of total blast exposures, there was significantly increased perfusion in the right middle/superior frontal gyri, supramarginal gyrus, lateral occipital cortex, and posterior cingulate cortex as well as bilateral anterior cingulate cortex, insulae, middle/superior temporal gyri and occipital poles. Examination of other neurotrauma and clinical variables such as close-range blast exposures, mTBI, and PTSD yielded no significant effects. These results raise the possibility that perfusion may be an important neural marker of brain health in blast exposure.     

The relationship of resting cerebral blood flow and brain activation during a social cognition task in adolescents with chronic moderate to severe traumatic brain injury: a preliminary investigation

Alterations in cerebrovascular function are evident acutely in moderate to severe traumatic brain injury (TBI), although less is known about their chronic effects. Adolescent and adult patients with moderate to severe TBI have been reported to demonstrate diffuse activation throughout the brain during functional magnetic resonance imaging (fMRI). Because fMRI is a measure related to blood flow, it is possible that any deficits in blood flow may alter activation. An arterial spin labeling (ASL) perfusion sequence was performed on seven adolescents with chronic moderate to severe TBI and seven typically developing (TD) adolescents during the same session in which they had performed a social cognition task during fMRI. In the TD group, prefrontal CBF was positively related to prefrontal activation and negatively related to non-prefrontal, posterior, brain activation. This relationship was not seen in the TBI group, who demonstrated a greater positive relationship between prefrontal CBF and non-prefrontal activation than the TD group. An analysis of CBF data independent of fMRI showed reduced CBF in the right non-prefrontal region (p<.055) in the TBI group. To understand any role reduced CBF may play in diffuse extra-activation, we then related the right non-prefrontal CBF to activation. CBF in the right non-prefrontal region in the TD group was positively associated with prefrontal activation, suggesting an interactive role of non-prefrontal and prefrontal blood flow throughout the right hemisphere in healthy brains. However, the TBI group demonstrated a positive association with activation constrained to the right non-prefrontal region. These data suggest a relationship between impaired non-prefrontal CBF and the presence of non-prefrontal extra-activation, where the region with more limited blood flow is associated with activation limited to that region. In a secondary analysis, pathology associated with hyperintensities on T2-weighted FLAIR imaging over the whole brain was related to whole brain activation, revealing a negative relationship between lesion volume and frontal activation, and a positive relationship between lesion volume and posterior activation. These preliminary data, albeit collected with small sample sizes, suggest that reduced non-prefrontal CBF, and possibly pathological tissue associated with T2-hyperintensities, may provide contributions to the diffuse, primarily posterior extra-activation observed in adolescents following moderate to severe TBI.     

Indomethacin: A review of its cerebral blood flow effects and potential use for controlling intracranial pressure in traumatic brain injury patients

Abstract

Traumatic brain injury (TBI) causes about 75,000 deaths and leaves approximately 200,000 people disabled in USA each year. Brain swelling and increased intracranial pressure (ICP) contribute to this morbidity and mortality. Aggressive management protocols,including ICP control, have been shown to reduce the overall mortality from 50% to 36% following severe head injury. Despite these encouraging results, new and improved pharmacologic strategies to control ICP are required. Indomethacin (IND) is a non-steroidal anti-inflammatory agent with unique effects on cerebral blood flow physiology which may be of benefit in reducing elevated ICP in TBI patients. Data from animal models and randomized, controlled studies with pre-term infants have shown that i.v. IND produces rapid, significant reductions in cerebral blood flow (CBF). Controlled studies of I.v. IND in normal volunteers show a reduction In CBF from 26%-40%. Case series involving severe TBI patients suggest that IND i.v. boluses of 30-50mg reduce ICP by 37%-52%, reduce CBF by 22%-26%, with a modest 14% increase in cerebral perfusion pressure (CPP). Despite these encouraging results, i.v. IND should only be considered an experimental treatment for control of refractory ICP in TBI patients. Larger, well-designed randomized trials in TBI patients will provide more efficacy and safety data and delineate the effects of IND alone or in combination with other proven, effective, or experimental therapies. Once these concerns have been addressed, larger outcome studies will ultimately be needed to determine the role of IND for ICP control in TBI patients. [Neurol Res 1999; 21: 491-499]     

Intensity-dependent regional cerebral blood flow during 1-Hz repetitive transcranial magnetic stimulation (rTMS) in healthy volunteers studied with H215O positron emission tomography: II. Effects of prefrontal cortex rTMS.

BACKGROUND: The changes in brain activity produced by repetitive transcranial magnetic stimulation (rTMS) of the prefrontal cortex (PFC) remain unclear. We examined intensity-related changes in brain activity with positron emission tomography (PET) in normal volunteers during rTMS delivered to the left PFC. METHODS: In 10 healthy volunteers, we delivered 1-Hz rTMS at randomized intensities over left PFC with a figure-eight coil. Intensities were 80, 90, 100, 110, and 120% of the right-hand muscle twitch threshold. Regional cerebral blood flow (rCBF) scans were acquired with H(2)(15)O PET during rTMS at each intensity. RESULTS: Repetitive transcranial magnetic stimulation intensity was inversely correlated with rCBF in the stimulated and contralateral PFC, ipsilateral medial temporal lobe, both parahippocampi, and posterior middle temporal gyri. Positive correlations of rCBF with intensity occurred in ipsilateral anterior cingulate, cerebellum, contralateral insula, primary auditory cortex, and somatosensory face area. CONCLUSIONS: The intensity-related inverse relationship between 1-Hz rTMS and prefrontal activity appears opposite to that seen with rTMS over the motor cortex in a companion study. Intensity-dependent increases in rCBF were seen in a number of distant cortical and subcortical areas with PFC rTMS, suggesting activation of left anterior cingulate, claustrum, and cerebellum. The regional differences in direction of rTMS effects and the greater activation of distant structures at higher intensities suggest the potential importance of higher-intensity prefrontal rTMS for therapeutic applications in neuropsychiatric patients.     

Cerebral blood flow in the ventromedial prefrontal cortex correlates with treatment response to low-frequency right prefrontal repetitive transcranial magnetic stimulation in the treatment of depression

Aims: Low‐frequency right prefrontal repetitive transcranial magnetic stimulation (rTMS) is effective in treating depression, and its antidepressant effects have proven to correlate with decreases in cerebral blood flow (CBF) in the orbitofrontal cortex and subgenual cingulate cortex. However, a predictor of treatment response to low‐frequency right prefrontal rTMS in depression has not been identified yet. The aim of this study was to estimate regional CBF in the frontal regions and investigate the correlation with treatment response to low‐frequency right prefrontal rTMS in depression. Methods: We examined 26 depressed patients for the correlation between treatment response to rTMS and regional CBF in the frontal regions, by analyzing their brain scans with ^99mTc‐ethyl cysteinate dimer before rTMS treatment. CBF in 16 brain regions was estimated using fully automated region of interest analysis software. Two principal components were extracted from CBF in 16 brain regions by factor analysis with maximum likelihood method and Promax rotation with Kaiser normalization. Results: Sixteen brain regions were divided into two groups: dorsolateral prefrontal cortex (superior frontal, medial frontal, middle frontal, and inferior frontal regions) and ventromedial prefrontal cortex (anterior cingulate, subcallosal, orbital, and rectal regions). Treatment response to rTMS was not correlated with CBF in the dorsolateral prefrontal cortex, but it was correlated with CBF in the ventromedial prefrontal cortex. Conclusion: These findings suggest that CBF in the ventromedial prefrontal cortex may be a potential predictor of low‐frequency right prefrontal rTMS, and depressed patients with increased CBF in the ventromedial prefrontal cortex may show a better response.     

Intensity-dependent regional cerebral blood flow during 1-Hz repetitive transcranial magnetic stimulation (rTMS) in healthy volunteers studied with H215O positron emission tomography: I. Effects of primary motor cortex rTMS.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) affects the excitability of the motor cortex and is thought to influence activity in other brain areas as well. We combined the administration of varying intensities of 1-Hz rTMS of the motor cortex with simultaneous positron emission tomography (PET) to delineate local and distant effects on brain activity. METHODS: Ten healthy subjects received 1-Hz rTMS to the optimal position over motor cortex (M1) for producing a twitch in the right hand at 80, 90, 100, 110, and 120% of the twitch threshold, while regional cerebral blood flow (rCBF) was measured using H(2)(15)O and PET. Repetitive transcranial magnetic stimulation (rTMS) was delivered in 75-pulse trains at each intensity every 10 min through a figure-eight coil. The regional relationship of stimulation intensity to normalized rCBF was assessed statistically. RESULTS: Intensity-dependent rCBF increases were produced under the M1 stimulation site in ipsilateral primary auditory cortex, contralateral cerebellum, and bilateral putamen, insula, and red nucleus. Intensity-dependent reductions in rCBF occurred in contralateral frontal and parietal cortices and bilateral anterior cingulate gyrus and occipital cortex. CONCLUSIONS: This study demonstrates that 1-Hz rTMS delivered to the primary motor cortex (M1) produces intensity-dependent increases in brain activity locally and has associated effects in distant sites with known connections to M1.