Resting-state Cerebral Blood Flow Research Articles

Nicotine and non-nicotine smoking factors differentially modulate craving, withdrawal and cerebral blood flow as measured with arterial spin labeling.

Smoking cessation results in withdrawal symptoms such as craving and negative mood that may contribute to lapse and relapse. Little is known regarding whether these symptoms are associated with the nicotine or non-nicotine components of cigarette smoke. Using arterial spin labeling, we measured resting-state cerebral blood flow (CBF) in 29 adult smokers across four conditions: (1) nicotine patch+denicotinized cigarette smoking, (2) nicotine patch+abstinence from smoking, (3) placebo patch+denicotinized cigarette smoking, and (4) placebo patch+abstinence from smoking. We found that changes in self-reported craving positively correlated with changes in CBF from the denicotinized cigarette smoking conditions to the abstinent conditions. These correlations were found in several regions throughout the brain. Self-reported craving also increased from the nicotine to the placebo conditions, but had a minimal relationship with changes in CBF. The results of this study suggest that the non-nicotine components of cigarette smoke significantly impact withdrawal symptoms and associated brain areas, independently of the effects of nicotine. As such, the effects of non-nicotine factors are important to consider in the design and development of smoking cessation interventions and tobacco regulation.

Age-related differences in cerebral blood flow underlie the BOLD fMRI signal in childhood.

Functional magnetic resonance imaging (fMRI) has become a premiere technique for studying the development and neural mediation of a wide range of typical and atypical behaviors in children. While the mechanism of the blood oxygen level-dependent (BOLD) fMRI signal has been a focus of investigation in the mature brain, it has been largely unexamined in the developing brain. One critical component of the BOLD signal that has been noted to change with age is cerebral blood flow (CBF). Reports of CBF in children based on clinical radioactive tracing methods have found elevated CBF in childhood relative to adulthood, which could affect the BOLD response. This study used non-invasive arterial spin labeling magnetic resonance imaging to study resting state and activity-driven CBF in conjunction with the functional BOLD response in healthy children 8 and 12 years of age and in adults. Participants performed a finger-tapping task to generate robust activation measured in the motor cortex. Quantification of resting state CBF demonstrated higher CBF in 8 year olds and in 12 year olds relative to adults. The absolute increase in CBF between baseline rest and peak response during the motor task was also higher in both child groups compared to adults. In contrast, the relative increase of CBF above baseline, expressed as percent of CBF change, was comparable across groups. The percent of BOLD signal change was also stable across age groups. This set of findings suggests that along with elevated CBF in childhood, other component processes of the BOLD response are also in an elevated state such that together they yield a net BOLD effect that resembles adults. These findings coincide with our previous examination of hemodynamics in primary sensory cortex. Although the magnitude of the BOLD response appears consistent between childhood and adulthood, the underlying physiology and cerebrovascular dynamics that give rise to the BOLD effect differ between immature and mature neural systems.

Developmental changes in resting and functional cerebral blood flow and their relationship to the BOLD response

Our understanding of cerebral blood flow (CBF) in the healthy developing brain has been limited due to the invasiveness of methods historically available for CBF measurement. Clinically based studies using radioactive tracers with children have focused on resting state CBF. Yet potential age-related changes in flow during stimulation may affect the blood oxygenation level dependent (BOLD) response used to investigate cognitive neurodevelopment. This study used noninvasive arterial spin labeling magnetic resonance imaging to compare resting state and stimulus-driven CBF between typically developing children 8 years of age, 12 years of age, and adults. Further, we acquired functional CBF and BOLD images simultaneously to examine their relationship during sensory stimulation. Analyses revealed age-related CBF differences during rest; the youngest group showed greater CBF than 12-year-olds or adults. During stimulation of the auditory cortex, younger children also showed a greater absolute increase in CBF than adults. However, the magnitude of CBF response above baseline was comparable between groups. Similarly, the amplitude of the BOLD response was stable across age. The combination of the 8 year olds' elevated CBF, both at rest and in response to stimulation, without elevation in the BOLD response suggests that additional physiological factors that also play a role in the BOLD effect, such as metabolic processes that are also elevated in this period, may offset the increased CBF in these children. Thus, CBF measurements reveal maturational differences in the hemodynamics underlying the BOLD effect in children despite the resemblance of the BOLD response between children and adults.

Resting-state cerebral blood flow in amygdala is modulated by sex and serotonin transporter genotype

Serotonin transporter-linked polymorphic region (5-HTTLPR) has been associated with modulation of resting-state amygdala level, which was considered to underlie a risk for mood and anxiety disorders. The findings however have been inconsistent which could be related to interactions of the genotype with other factors e.g. sex or personality characteristics. Therefore, the aim of the present study was to explore the modulation of the amygdala perfusion in the resting-state by sex and 5-HTTLPR/rs25531 genotype, controlled for personality dimensions assessed by Temperament and Character Inventory (Cloninger et al., 1994). The resting-state cerebral blood flow (rCBF) was examined using an arterial spin labelling technique. All participants were genotyped for the 5-HTTLPR/rs25531 genotype (L/L-L/S-S/S genotypes and LA-LG variants). The study group comprised 81 right-handed Caucasian healthy volunteers (42 females) aged 19-55 years. We measured rCBF in the amygdala and in the whole-brain grey matter. The data of blood-oxygen-level-dependent (BOLD) response in amygdala to fearful dynamic faces in the same sample were also analysed. There was a significant main effect of sex in both the left and right amygdalae, with higher rCBF in males. Main effect of 5-HTTLPR/rs25531 genotype which was significant in the right amygdala only, was accounted for by higher rCBF in S/S vs. L/L homozygotes. An interaction between sex and 5-HTTLPR/rs25531 genotype was observed in rCBF in the right amygdala. This was accounted for by higher values of rCBF in the right amygdala in males' S allele carriers compared with females. In females, there was a significant negative correlation between the rCBF and BOLD response in the right amygdala, and more so in S carriers. In males, there was no significant correlation between rCBF and BOLD response in the right amygdala. The novelty of our results lies in the demonstration of gene by sex interaction with resting blood flow in the amygdala that elucidates sex-related differences in emotional reactivity.

Reduced Cerebral Blood Flow Within the Default-Mode Network and Within Total Gray Matter in Major Depression

The default-mode network (DMN) was shown to have aberrant blood oxygenation-level-dependent (BOLD) activity in major depressive disorder (MDD). While BOLD is a relative measure of neural activity, cerebral blood flow (CBF) is an absolute measure. Resting-state CBF alterations have been reported in MDD. However, the association of baseline CBF and CBF fluctuations is unclear in MDD. Therefore, the aim was to investigate the CBF within the DMN in MDD, applying a strictly data-driven approach. In 22 MDD patients and 22 matched healthy controls, CBF was acquired using arterial spin labeling (ASL) at rest. A concatenated independent component analysis was performed to identify the DMN within the ASL data. The perfusion of the DMN and its nodes was quantified and compared between groups. The DMN was identified in both groups with high spatial similarity. Absolute CBF values within the DMN were reduced in MDD patients (p<0.001). However, after controlling for whole-brain gray matter CBF and age, the group difference vanished. In patients, depression severity was correlated with reduced perfusion in the DMN in the posterior cingulate cortex and the right inferior parietal lobe. Hypoperfusion within the DMN in MDD is not specific to the DMN. Still, depression severity was linked to DMN node perfusion, supporting a role of the DMN in depression pathobiology. The finding has implications for the interpretation of BOLD functional magnetic resonance imaging data in MDD.

Resting State Abnormalities in Psychosis Compared to Acute Cannabinoids and Opioids Challenges: A Systematic Review of Functional Imaging Studies

We conducted a systematic review on resting state cerebral blood flow activities found in first-episode psychosis (FEP) and during acute effects of cannabinoids and opioids, mental states that can be profoundly different from normal functioning. The main goal was to identify connections of cerebral blood flow measure and regional brain activity patterns associated with subjective experiences and to find out whether there are similarities between the three mental states. The present study reviewed systematically the current state of research with respect to cannabinoids and opioids on resting state activity patterns as investigated by different neuroimaging techniques. Twenty-two studies encompassing different neuroimaging techniques were selected. Cerebral perfusion and resting blood flow measure by single-photon emission computed tomography (SPECT), positron emission tomography (PET), perfusion-weighted imaging (PWI), arterial spin labeling (ASL), and resting-state functional magnetic resonance imaging (resting-state fMRI) during acute cannabinoids or opioids challenges were compared to findings in patients with FEP. The total number of subjects included in this review encompassed 279 FEP/controls (mean age = 28 ± 8.6 years, 40.1% females), 315 participants with cannabinoids (mean age = 29 ± 7.1 years, 31.8% females) and 113 participants with opioids (mean age = 30 ± 3.9 years, 17.3% females). We found that effects on regional activity were highly conflicting within the same condition group. However, we critical compared baseline acitivty patterns between FEP and acute cannabinoid or opioids effects. There was some consistent evidence suggesting positive symptoms of FEP and depersonalization experiences after cannabis administration both result in an increased anterior cingulate activity, an important area in the default mode network.

Extrauterine environment influences spontaneous low-frequency oscillations in the preterm brain

Low-frequency oscillations in cerebral blood flow that are suggestive of resting-state brain activity have recently been reported, but no study on the development of resting-state brain activity in preterm infants has been performed. The objective of this study was to measure the cerebral blood flow oscillations, which are assumed to represent brain function in the resting state, in preterm and term infants of the same postconceptional age. The subjects were 9 preterm infants who had reached full term (gestational age (GA): 23–34weeks, postconceptional age: 37–46weeks) and 10 term infants (GA: 37–40weeks, postconceptional age: 37–41weeks). Their changes in concentration of oxyhemoglobin ([oxyHb]) and deoxyhemoglobin ([deoxyHb]) were measured in the parieto-temporal region during quiet sleep using multi-channel near-infrared spectroscopy, and the power spectral densities (PSD) of the oscillations in the concentrations of these molecules were analyzed and compared. The preterm infants displayed a higher proportion of 0.06–0.10Hz low frequency oscillations of [oxyHb] and [deoxyHb] than the term infants, and the gestational age and the proportion of low frequency oscillations were inversely correlated. These findings suggest that resting-state cerebral blood flow oscillations differ between preterm and term infants, and that the development of circulatory regulation and nerve activity in preterm infants are influenced by the extrauterine environment.

Baseline Cardiovascular Risk Predicts Subsequent Changes in Resting Brain Function

The Framingham Heart Study group cardiovascular disease risk profile (FCRP) score was used to assess the relationship between baseline cardiovascular risk and subsequent changes in resting state cerebral blood flow (CBF) in cognitively normal older participants from the Baltimore Longitudinal Study of Aging. Ninty-seven cognitively normal participants underwent annual resting-state positron emission tomography scans at baseline and over a period of up to 8 years (mean interval, 7.4 years). Images quantifying voxel-wise longitudinal rates of CBF change were calculated and used to examine the relationship between baseline FCRP score and changes over time in regional CBF. Individual components of the FCRP score (age, cholesterol, blood pressure, smoking status, and type 2 diabetes) were also correlated with changes in regional CBF to examine the independent contributions of each component to the overall pattern of change. Higher baseline FCRP scores were associated with accelerated longitudinal decline in CBF in orbitofrontal, medial frontal/anterior cingulate, insular, precuneus, and brain stem regions. Of the components that comprise the FCRP score, higher diastolic blood pressure and diabetes were associated independently with greater decline in the medial frontal/anterior cingulate and insular regions, respectively. Baseline cardiovascular risk factors are associated with greater rates of decline in resting state regional brain function. The regions showing accelerated decline participate in higher-order cognitive processes and are also vulnerable to age-related neuropathology. These results, in conjunction with other studies, encourage early treatment of cardiovascular risk factors in older individuals.

The Effects of Dietary Caffeine Use and Abstention on Blood Oxygen Level-Dependent Activation and Cerebral Blood Flow.

Caffeine is a known vasoconstrictor that reduces resting cerebral blood flow (CBF) throughout the brain. This effect may be problematic in functional magnetic resonance imaging (fMRI) research, as the blood oxygen level-dependent (BOLD) signal is a complex interaction of CBF and other factors that are dependent on changes in neural activity. It is unknown whether changes in the BOLD signal during an fMRI experiment could be affected by subjects' recent use or abstinence from dietary caffeine. Here, we report two similar studies (n=45 and 17) that measure the effects of caffeine on BOLD activation, BOLD time course parameters, and CBF. Using a factorial design, low, moderate, and high caffeine consumers received either caffeine (250 mg) or placebo during normal caffeine use (satiated state) or after 30 hours of abstention (abstinent state). The fMRI of a reaction time task and resting-state CBF were collected. In general, acute caffeine administration reduced the time to peak and full width at half maximum of the BOLD time course, and CBF across both studies. Caffeine also produced a small reduction in BOLD activation. The majority of these reductions across measures were moderated by neither the level of caffeine use, nor the abstinent or satiated state. These results suggest that dietary caffeine use does not produce a significant effect on task-related BOLD activation.

Genetic modulation of neural response during working memory in healthy individuals: interaction of glucocorticoid receptor and dopaminergic genes

Suboptimal performance in working memory (WM) tasks and inefficient prefrontal cortex functioning are related to dysregulation of dopaminergic (DA) and hypothalamic-pituitary-adrenal systems. The aim of the present study was to investigate the joint effect of genetic polymorphisms coding for DA catabolism and glucocorticoid receptor (GR, NR3C1) on brain functioning. The study group (90 right-handed white Caucasian healthy individuals) underwent functional magnetic resonance imaging experiments to examine blood oxygenation level dependent (BOLD) response during a WM task with varying cognitive load (1-, 2- and 3-back). We have also examined skin conductance response (SCR) during the WM task and resting-state cerebral blood flow with continuous arterial spin labelling. The genetic markers of interest included Catechol-O-Methyl-Transferase (COMT) (Met(158)Val) and NR3C1 single-nucleotide polymorphisms (BclI C/G rs41423247, 9β A/G rs6198 and rs1866388 A/G). Haplotype-based analyses showed (i) a significant effect of COMT polymorphism on left anterior cingulate cortex, with greater deactivation in Met carriers than in Val/Val homozygotes; (ii) a significant effect of BclI polymorphism on right dorsolateral prefrontal cortex (DLPFC), with greater activation in G/G carriers than in C carriers and (iii) an interactive effect of BclI (G/G) and COMT (Met/Met) polymorphisms, which was associated with greater activation in right DLPFC. These effects remained significant after controlling for whole-brain resting-state blood flow. SCR amplitude was positively correlated with right DLPFC activation during WM. This study demonstrated that GR and COMT markers exert their separate, as well as interactive, effects on DLPFC function. Epistasis of COMT and BclI minor alleles is associated with higher activation, suggesting lower efficiency, of DLPFC during WM.

Neural correlates of disbalanced motor control in major depression

Motor retardation is a common symptom of major depressive disorder (MDD). Despite the existence of various assessment methods, little is known on the pathobiology of motor retardation. We aimed to elucidate aspects of motor control investigating the association of objective motor activity and resting state cerebral blood flow (CBF). Nineteen control subjects and 20 MDD patients were investigated using arterial spin labeling (ASL) at 3T in the morning to quantify resting state CBF. Afterwards wrist actigraphy was recorded for 24h. CBF, group and activity level (AL) were entered into a whole brain general linear model. MDD patients had reduced AL. Both groups had linear associations of AL and CBF in bilateral rostral prefrontal cortex. Groups differed in four clusters associated with motor control. In controls a positive association was found in the left caudal cingulate zone (CCZ) and an inverse association in the right external globus pallidus (GPe). MDD patients had positive associations in the right orbitofrontal cortex and inverse associations in the left supplemental motor area. Patients were on antidepressant medication. The pattern of associations between CBF and AL suggest disbalanced motor control in MDD. Findings are in line with the hypothesis of dopamine deficits contributing to motor retardation in MDD.

Magnetic resonance perfusion imaging of resting-state cerebral blood flow in preclinical Huntington's disease

Magnetic resonance imaging (MRI) of the brain could be a powerful tool for discovering early biomarkers in clinically presymptomatic carriers of the Huntington's disease gene mutation (preHD). The aim of this study was to investigate the sensitivity of resting-state perfusion MRI in preHD and to identify neural changes, which could serve as biomarkers for future clinical trials. Differences in regional cerebral blood flow (rCBF) in 18 preHD and 18 controls were assessed with a novel MRI method based on perfusion images obtained with continuous arterial spin labeling. High-resolution structural data were collected to test for changes of brain volume. Compared with controls, preHD individuals showed decreased rCBF in medial and lateral prefrontal regions and increased rCBF in the precuneus. PreHD near to symptom onset additionally showed decreased rCBF in the putamen and increased rCBF in the hippocampus. Network analyses revealed an abnormal lateral prefrontal pattern in preHD far and near to motor onset. These data suggest early changes of frontostriatal baseline perfusion in preHD independent of substantial reductions of gray matter volume. This study also shows the feasibility of detecting neural changes in preHD with a robust MRI technique that would be suitable for longitudinal multisite application.

Resting state cerebral blood flow and objective motor activity reveal basal ganglia dysfunction in schizophrenia

Reduced motor activity has been reported in schizophrenia and was associated with subtype, psychopathology and medication. Still, little is known about the neurobiology of motor retardation. To identify neural correlates of motor activity, resting state cerebral blood flow (CBF) was correlated with objective motor activity of the same day. Participants comprised 11 schizophrenia patients and 14 controls who underwent magnetic resonance imaging with arterial spin labeling and wrist actigraphy. Patients had reduced activity levels and reduced perfusion of the left parahippocampal gyrus, left middle temporal gyrus, right thalamus, and right prefrontal cortex. In controls, but not in schizophrenia, CBF was correlated with activity in the right thalamic ventral anterior (VA) nucleus, a key module within basal ganglia-cortical motor circuits. In contrast, only in schizophrenia patients positive correlations of CBF and motor activity were found in bilateral prefrontal areas and in the right rostral cingulate motor area (rCMA). Grey matter volume correlated with motor activity only in the left posterior cingulate cortex of the patients. The findings suggest that basal ganglia motor control is impaired in schizophrenia. In addition, CBF of cortical areas critical for motor control was associated with volitional motor behavior, which may be a compensatory mechanism for basal ganglia dysfunction.

Abnormal resting state corticolimbic blood flow in depressed unmedicated patients with major depression: A 15O‐H2O PET study

We investigated the differences in the resting state corticolimbic blood flow between 20 unmedicated depressed patients and 21 healthy comparisons. Resting state cerebral blood flow (CBF) was measured with H(2)(15)O PET. Anatomical MRI scans were performed on an Elscint 1.9 T Prestige system for PET-MRI coregistration. Significant changes in cerebral blood flow indicating neural activity were detected using an ROI-free image subtraction strategy. In addition, the resting blood flow in patients was correlated with the severity of depression as measured by HAM-D scores. Depressed patients showed decreases in blood flow in right anterior cingulate (Brodmann areas 24 and 32) and increased blood flow in left and right posterior cingulate (Brodmann areas 23, 29, 30), left parahippocampal gyrus (Brodmann area 36), and right caudate compared with healthy volunteers. The severity of depression was inversely correlated with the left middle and inferior frontal gyri (Brodmann areas 9 and 47) and right medial frontal gyrus (Brodmann area 10) and right anterior cingulate (Brodmann areas 24, 32) blood flow, and directly correlated with the right thalamus blood flow. These findings support previous reports of abnormalities in the resting state blood flow in the limbic-frontal structures in depressed patients compared to healthy volunteers.

Alterations in Cerebral Metabolic Rate and Blood Supply across the Adult Lifespan

With age, the brain undergoes comprehensive changes in its function and physiology. Cerebral metabolism and blood supply are among the key physiologic processes supporting the daily function of the brain and may play an important role in age-related cognitive decline. Using MRI, it is now possible to make quantitative assessment of these parameters in a noninvasive manner. In the present study, we concurrently measured cerebral metabolic rate of oxygen (CMRO(2)), cerebral blood flow (CBF), and venous blood oxygenation in a well-characterized healthy adult cohort from 20 to 89 years old (N = 232). Our data showed that CMRO(2) increased significantly with age, while CBF decreased with age. This combination of higher demand and diminished supply resulted in a reduction of venous blood oxygenation with age. Regional CBF was also determined, and it was found that the spatial pattern of CBF decline was heterogeneous across the brain with prefrontal cortex, insular cortex, and caudate being the most affected regions. Aside from the resting state parameters, the blood vessels' ability to dilate, measured by cerebrovascular reactivity to 5% CO(2) inhalation, was assessed and was reduced with age, the extent of which was more prominent than that of the resting state CBF.

Resting Cerebral Blood Flow Alterations in Chronic Traumatic Brain Injury: An Arterial Spin Labeling Perfusion fMRI Study

Non-invasive measurement of resting state cerebral blood flow (CBF) may reflect alterations of brain structure and function after traumatic brain injury (TBI). However, previous imaging studies of resting state brain in chronic TBI have been limited by several factors, including measurement in relative rather than absolute units, use of crude spatial registration methods, exclusion of subjects with substantial focal lesions, and exposure to ionizing radiation, which limits repeated assessments. This study aimed to overcome those obstacles by measuring absolute CBF with an arterial spin labeling perfusion fMRI technique, and using an image preprocessing protocol that is optimized for brains with mixed diffuse and focal injuries characteristic of moderate and severe TBI. Resting state CBF was quantified in 27 individuals with moderate to severe TBI in the chronic stage, and 22 demographically matched healthy controls. In addition to global CBF reductions in the TBI subjects, more prominent regional hypoperfusion was found in the posterior cingulate cortices, the thalami, and multiple locations in the frontal cortices. Diffuse injury, as assessed by tensor-based morphometry, was mainly associated with reduced CBF in the posterior cingulate cortices and the thalami, where the greatest volume losses were detected. Hypoperfusion in superior and middle frontal cortices, in contrast, was associated with focal lesions. These results suggest that structural lesions, both focal and diffuse, are the main contributors to the absolute CBF alterations seen in chronic TBI, and that CBF may serve as a tool to assess functioning neuronal volume. We also speculate that resting reductions in posterior cingulate perfusion may reflect alterations in the default-mode network, and may contribute to the attentional deficits common in TBI.

P02-159 - Magnetic resonance imaging of baseline brain perfusion in major depressive disorder

IntroductionContinuous arterial spin labelling (cASL) is a non-invasive magnetic resonance imaging method increasingly used to study human brain function and perfusion physiology.ObjectivesIn this study, we investigated distinct patterns of cerebral blood flow (CBF) in MDD patients by means of resting state cASL.Methods11 healthy controls and 11 patients with MDD according to DSM-IV criteria were included. The individual cASL images underwent data preprocessing steps including the generation of perfusion-weighted images, followed by conversion to quantified CBF. An analysis of temporally coherent CBF patterns was performed using a spatial Independent Component Analysis.ResultsBoth groups showed distinct blood flow patterns in a medial frontoparietal and lateral temporal component (“default mode” network), a medial temporal and anterior cingulate component (“limbic” network) and bilateral prefrontal and parietal component (“cognitive” network). Within the “limbic” network, MDD patients showed a pattern of increased CBF in the bilateral ventrolateral prefrontal, cingulate, striatal and hippocampal regions. Within the “cognitive” network, MDD patients showed a pattern of increased CBF in left dorsolateral prefrontal and the inferior parietal areas. Decreased perfusion in MDD patients was found in the right precuneus, the right inferior parietal cortex, the left posterior cingulate and the left lateral temporal cortex.ConclusionsThese preliminary data demonstrate the sensitivity of cASL techniques for detecting resting state CBF changes in MDD patients. Thus, cASL studies in MDD could provide valuable information with regard to neurobiologically characterized endophenotypes, while resting state CBF measures could serve as objective predictors of treatment response in future studies.

An Investigation of Static and Dynamic Characteristics of Resting-State Cerebral Blood Flow

An Investigation of Static and Dynamic Characteristics of Resting-State Cerebral Blood Flow

Clinical and cerebral activity changes induced by subthalamic nucleus stimulation in advanced Parkinson's disease: A prospective case-control study

Background High-frequency stimulation of the subthalamic nucleus (STN-DBS) improves motor symptoms in advanced Parkinson's disease (PD), but the mechanisms are still unclear. Functional imaging evidenced pathological overactivity in motor cortical areas in advanced PD that can be normalized by effective therapies. Patients and methods We studied resting state cerebral blood flow pre-operatively and 12 months after surgery in 40 patients with advanced PD using ECD-SPECT. SPECT scans were also acquired 1 year apart in 21 matched PD controls who did not undergo surgery. Statistical analysis was performed using statistical parametric mapping (SPM2) software. In addition, we correlated brain perfusion changes after surgery with clinical improvement, assessed using the unified PD rating scale motor score (UPDRS-III). Results Patients showed marked motor improvement and medication reduction after surgery. Stimulated PD patients revealed bilateral rCBF decrements in motor cortical areas and prefrontal cortex bilaterally compared to pre-surgical condition as well as versus PD controls ( p < .01 FDR corrected). Perfusion increases were found in cerebellum, temporal and occipital lobes. Clinical improvement was associated with perfusion decrements in primary motor and premotor cortices. Conclusions Effective STN-DBS is associated with neuronal activity changes in brain regions implicated in movement programming and performance. We hypothesize that clinical benefit might be associated with stimulation-induced normalization of the abnormal overactivity within the cortico-basal ganglia-thalamo-cortical motor loop in advanced PD.

Differential age effects on cerebral blood flow and BOLD response to encoding: Associations with cognition and stroke risk

Changes in the cerebrovascular system due to age or disease can significantly alter the blood-oxygenation-level-dependent (BOLD) signal and complicate its interpretation. The simultaneous acquisition of arterial spin labeling (ASL) and BOLD data represents a useful technique to more fully characterize the neurovascular underpinnings of functional brain response to cognition. We conducted a functional magnetic resonance imaging (FMRI) study of episodic memory encoding to investigate whether age is related to cerebral blood flow (CBF) and BOLD response in the medial temporal lobe (MTL). Results demonstrated a significant reduction in resting-state CBF in older compared to young adults. Conversely, older adults showed significantly increased CBF but not BOLD response in the MTL during picture encoding relative to young adults. Correlations between CBF response and cognition were demonstrated whereas associations with BOLD were not observed. Stroke risk was associated with both CBF and BOLD response. Results suggest that aging effects on CBF and BOLD responses to encoding are dissociable and that cerebrovascular alterations contribute to findings of age-related differences.