Effects of route of administration on oxytocin-induced changes in regional cerebral blood flow in humans.

Could nose-to-brain pathways mediate the effects of peptides such as oxytocin (OT) on brain physiology when delivered intranasally? We address this question by contrasting two methods of intranasal administration (a standard nasal spray, and a nebulizer expected to improve OT deposition in nasal areas putatively involved in direct nose-to-brain transport) to intravenous administration in terms of effects on regional cerebral blood flow during two hours post-dosing. We demonstrate that OT-induced decreases in amygdala perfusion, a key hub of the OT central circuitry, are explained entirely by OT increases in systemic circulation following both intranasal and intravenous OT administration. Yet we also provide robust evidence confirming the validity of the intranasal route to target specific brain regions. Our work has important translational implications and demonstrates the need to carefully consider the method of administration in our efforts to engage specific central oxytocinergic targets for the treatment of neuropsychiatric disorders.

Acúmulo de 131INa en quistes renales sin relación con enfermedad metastásica en un paciente con carcinoma diferenciado de tiroides / Accumulation of 131INa activity in renal cysts unrelated to metastatic disease in a patient with differentiated thyroid cancer

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Phenomenologically distinct psychotomimetic effects of ketamine are associated with cerebral blood flow changes in functionally relevant cerebral foci: a continuous arterial spin labelling study.

RATIONALE: The N-methyl-D-aspartate (NMDA) receptor antagonist ketamine provides a pragmatic approach to address the link between glutamate-mediated changes in brain function and psychosis-like experiences. Most studies using PET or BOLD fMRI have assessed these symptoms broadly, which may limit inference about specific mechanisms. OBJECTIVES: The objective of this study is to identify the cerebral blood flow (CBF) correlates of ketamine-induced psychopathology, focusing on individual psychotomimetic symptom dimensions, which may have separable neurobiological substrates. METHODS: We measured validated psychotomimetic symptom factors following intravenous ketamine administration in 23 healthy male volunteers (10 given a lower dose and 13 a higher dose) and correlated ketamine-induced changes in symptoms with regional changes in CBF, measured non-invasively using arterial spin labelling (ASL). RESULTS: The main effect of ketamine paralleled previous studies, with increases in CBF in anterior and subgenual cingulate cortex and decreases in superior and medial temporal cortex. Subjective effects were greater in the high-dose group. For this group, ketamine-induced anhedonia inversely related to orbitofrontal cortex CBF changes and cognitive disorganisation was positively correlated with CBF changes in posterior thalamus and the left inferior and middle temporal gyrus. Perceptual distortion was correlated with different regional CBF changes in the low- and high-dose groups. CONCLUSIONS: Here, we provide evidence for the sensitivity of ASL to the effects of ketamine and the strength of subjective experience, suggesting plausible neural mechanisms for ketamine-induced anhedonia and cognitive disorganisation.

SPECT-TC con 111In-octreotide en paragangliomas de cabeza y cuello / 111In-octreotide SPECT-CT in head and neck paragangliomas

Los paragangliomas de cabeza y cuello son tumores neuroendocrinos poco frecuentes, que expresan receptores para la somatostatina (RSS) en su superficie celular, particularmente el subtipo 2. Por esta particularidad, en la Medicina Nuclear es posible obtener imágenes de los mismos mediante la utilización de análogos sintéticos de la somatostatina, principalmente el octreotide, el cual tras su radiomarcaje con 111In o 68Ga, permiten su visualización selectiva, bien por imágenes gammagráficas planares, SPECT-TC o PET-TC. De una serie de pacientes se seleccionan y presentan 3 casos que ilustran la utilidad de los estudios SPECT-TC con 111In-octreotide en el diagnóstico y seguimiento de este tipo de tumor: caracterización y diagnóstico inicial, estadificación y detección de recurrencia local o metástasis, y su valor añadido respecto a las imágenes anatómicas (resonancia magnética, tomografía computarizada, angiografía), por ejemplo en la diferenciación entre tejido funcional o cicatricial en los pacientes sometidos previamente a cirugía (AU)

Head and neck paragangliomas are rare neuroendocrine tumors expressing somatostatin receptors on their cell surface, particularly subtype 2. Due to this distinctive feature, images can be obtained in Nuclear Medicine using synthetic analogues of somatostatin, mainly octreotide, which allow selective display by planar scintigraphy, SPECT-CT or PET-CT imaging after radiolabeling with 111In or 68Ga. Three cases have been selected and presented from a series of patients that illustrate the utility of SPECT-CT studies with 111In-octreotide in the diagnosis and monitoring of this type of tumor. These are characterization at initial diagnosis, staging, and detection of local recurrence or metastasis, with added value with respect to anatomical images (nuclear magnetic resonance, computed axial tomography, angiography), for example in the differentiation between functional tissue or scar in patients who had previously undergone surgery (AU)

(111)In-octreotide SPECT-CT in head and neck paragangliomas.

Head and neck paragangliomas are rare neuroendocrine tumors expressing somatostatin receptors on their cell surface, particularly subtype 2. Due to this distinctive feature, images can be obtained in Nuclear Medicine using synthetic analogues of somatostatin, mainly octreotide, which allow selective display by planar scintigraphy, SPECT-CT or PET-CT imaging after radiolabeling with (111)In or (68)Ga. Three cases have been selected and presented from a series of patients that illustrate the utility of SPECT-CT studies with (111)In-octreotide in the diagnosis and monitoring of this type of tumor. These are characterization at initial diagnosis, staging, and detection of local recurrence or metastasis, with added value with respect to anatomical images (nuclear magnetic resonance, computed axial tomography, angiography), for example in the differentiation between functional tissue or scar in patients who had previously undergone surgery.

Gradient induced artifacts in simultaneous EEG-fMRI: Effect of synchronization on spiral and EPI k-space trajectories.

The nature of the gradient induced electroencephalography (EEG) artifact is analyzed and compared for two functional magnetic resonance imaging (fMRI) pulse sequences with different k-space trajectories: echo planar imaging (EPI) and spiral. Furthermore, the performance of the average artifact subtraction algorithm (AAS) to remove the gradient artifact for both sequences is evaluated. The results show that the EEG gradient artifact for spiral sequences is one order of magnitude higher than for EPI sequences due to the chirping spectrum of the spiral sequence and the dB/dt of its crusher gradients. However, in the presence of accurate synchronization, the use of AAS yields the same artifact suppression efficiency for both pulse sequences below 80Hz. The quality of EEG signal after AAS is demonstrated for phantom and human data. EEG spectrogram and visual evoked potential (VEP) are compared outside the scanner and use both EPI and spiral pulse sequences. MR related artifact residues affect the spectra over 40Hz (less than 0.2 µV up to 120Hz) and modify the amplitude of P1, N2 and P300 in the VEP. These modifications in the EEG signal have to be taken into account when interpreting EEG data acquired in simultaneous EEG-fMRI experiments.

Ageing diminishes the modulation of human brain responses to visual food cues by meal ingestion.

BACKGROUND/OBJECTIVES: Rates of obesity are greatest in middle age. Obesity is associated with altered activity of brain networks sensing food-related stimuli and internal signals of energy balance, which modulate eating behaviour. The impact of healthy mid-life ageing on these processes has not been characterised. We therefore aimed to investigate changes in brain responses to food cues, and the modulatory effect of meal ingestion on such evoked neural activity, from young adulthood to middle age. SUBJECTS/METHODS: Twenty-four healthy, right-handed subjects, aged 19.5-52.6 years, were studied on separate days after an overnight fast, randomly receiving 50 ml water or 554 kcal mixed meal before functional brain magnetic resonance imaging while viewing visual food cues. RESULTS: Across the group, meal ingestion reduced food cue-evoked activity of amygdala, putamen, insula and thalamus, and increased activity in precuneus and bilateral parietal cortex. Corrected for body mass index, ageing was associated with decreasing food cue-evoked activation of right dorsolateral prefrontal cortex (DLPFC) and precuneus, and increasing activation of left ventrolateral prefrontal cortex (VLPFC), bilateral temporal lobe and posterior cingulate in the fasted state. Ageing was also positively associated with the difference in food cue-evoked activation between fed and fasted states in the right DLPFC, bilateral amygdala and striatum, and negatively associated with that of the left orbitofrontal cortex and VLPFC, superior frontal gyrus, left middle and temporal gyri, posterior cingulate and precuneus. There was an overall tendency towards decreasing modulatory effects of prior meal ingestion on food cue-evoked regional brain activity with increasing age. CONCLUSIONS: Healthy ageing to middle age is associated with diminishing sensitivity to meal ingestion of visual food cue-evoked activity in brain regions that represent the salience of food and direct food-associated behaviour. Reduced satiety sensing may have a role in the greater risk of obesity in middle age.

Association of placental perfusion, as assessed by magnetic resonance imaging and uterine artery Doppler ultrasound, and its relationship to pregnancy outcome.

PURPOSE: To investigate (a) if placental perfusion in the second trimester of pregnancy, measured by two non-invasive magnetic resonance imaging (MRI) techniques, is related to impedance to flow in the uterine arteries, as assessed by Doppler ultrasound; and (b) if these measures are associated with future gestational outcome. METHODS: In 37 singleton pregnancies at 24-29 weeks' gestation, uterine artery pulsatility index (PI) was measured by Doppler ultrasound and placental perfusion was measured by Arterial Spin Labelling (flow-sensitive alternating inversion recovery (FAIR)) and intravoxel incoherent motion (IVIM) echo-planar imaging at 1.5 T in basal, central and placental regions of interest. The values were compared between those delivering small for gestational age (SGA) and appropriate for gestational age (AGA) neonates. RESULTS: In 23 pregnancies that resulted in delivery of SGA neonates, compared to the 14 with AGA neonates, the median basal FAIR measure was significantly lower (923.0 vs. 2359.0 arbitrary units; p = 0.003) as were IVIM measures of perfusing fraction (f) in basal, central and whole-placental regions (37.8 vs. 40.7%; p = 0.046; 24.3 vs. 35.1%; p = 0.014 and 27.9% vs. 36.2%; p = 0.001, respectively). In the SGA group, the median uterine artery PI was increased (1.96 vs. 1.03; p = 0.001). There were significant associations between uterine artery PI and placental perfusion assessed by both FAIR and IVIM. CONCLUSION: Pregnancies that result in SGA neonates exhibited reduced placental perfusion as assessed by MRI during the second trimester. This measurement was found to be strongly associated with impedance to flow in the uterine arteries. We suggest that FAIR or IVIM MRI examinations may be used to directly and non-invasively determine placental perfusion, and that the measured values are strong indicators of future gestational outcome.

Multivariate decoding of brain images using ordinal regression.

Neuroimaging data are increasingly being used to predict potential outcomes or groupings, such as clinical severity, drug dose response, and transitional illness states. In these examples, the variable (target) we want to predict is ordinal in nature. Conventional classification schemes assume that the targets are nominal and hence ignore their ranked nature, whereas parametric and/or non-parametric regression models enforce a metric notion of distance between classes. Here, we propose a novel, alternative multivariate approach that overcomes these limitations - whole brain probabilistic ordinal regression using a Gaussian process framework. We applied this technique to two data sets of pharmacological neuroimaging data from healthy volunteers. The first study was designed to investigate the effect of ketamine on brain activity and its subsequent modulation with two compounds - lamotrigine and risperidone. The second study investigates the effect of scopolamine on cerebral blood flow and its modulation using donepezil. We compared ordinal regression to multi-class classification schemes and metric regression. Considering the modulation of ketamine with lamotrigine, we found that ordinal regression significantly outperformed multi-class classification and metric regression in terms of accuracy and mean absolute error. However, for risperidone ordinal regression significantly outperformed metric regression but performed similarly to multi-class classification both in terms of accuracy and mean absolute error. For the scopolamine data set, ordinal regression was found to outperform both multi-class and metric regression techniques considering the regional cerebral blood flow in the anterior cingulate cortex. Ordinal regression was thus the only method that performed well in all cases. Our results indicate the potential of an ordinal regression approach for neuroimaging data while providing a fully probabilistic framework with elegant approaches for model selection.

Association of placental T2 relaxation times and uterine artery Doppler ultrasound measures of placental blood flow.

PURPOSE: To investigate whether, in the second trimester of pregnancy, placental T2 relaxation time (determined using magnetic resonance imaging (MRI)) is related to impedance to flow in the uterine arteries. METHODS: In 40 singleton pregnancies at 24-29 weeks' gestation, uterine artery pulsatility index (PI) was measured by Doppler ultrasound and T2 relaxation time was measured by echo planar MRI at 1.5 T. The significance of the associations between T2 relaxation time, uterine artery PI and birth weight were examined. RESULTS: In 25 pregnancies that delivered small for gestational age (SGA) neonates with birth weight below the 10th percentile, compared to those with appropriate for gestational age (AGA) birth weight, the T2 relaxation time was significantly decreased (88 ms vs. 149 ms, p < 0.0001) and uterine artery PI was increased (1.96 vs. 1.00, p < 0.0001). There were significant associations between placental T2 relaxation time and log10 uterine artery PI (r = -0.749, p < 0.0001), and between T2 relaxation and birth weight percentile (r = 0.693, p < 0.0001). CONCLUSION: The T2 relaxation time during the second trimester is shorter in pregnancies that subsequently deliver SGA neonates and the measurement is strongly correlated with impedance to flow in the uterine arteries.

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.

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, 9ß 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 visuospatial working memory in the 'at-risk mental state'.

BACKGROUND: Impaired spatial working memory (SWM) is a robust feature of schizophrenia and has been linked to the risk of developing psychosis in people with an at-risk mental state (ARMS). We used functional magnetic resonance imaging (fMRI) to examine the neural substrate of SWM in the ARMS and in patients who had just developed schizophrenia. METHOD: fMRI was used to study 17 patients with an ARMS, 10 patients with a first episode of psychosis and 15 age-matched healthy comparison subjects. The blood oxygen level-dependent (BOLD) response was measured while subjects performed an object-location paired-associate memory task, with experimental manipulation of mnemonic load. RESULTS: In all groups, increasing mnemonic load was associated with activation in the medial frontal and medial posterior parietal cortex. Significant between-group differences in activation were evident in a cluster spanning the medial frontal cortex and right precuneus, with the ARMS groups showing less activation than controls but greater activation than first-episode psychosis (FEP) patients. These group differences were more evident at the most demanding levels of the task than at the easy level. In all groups, task performance improved with repetition of the conditions. However, there was a significant group difference in the response of the right precuneus across repeated trials, with an attenuation of activation in controls but increased activation in FEP and little change in the ARMS. CONCLUSIONS: Abnormal neural activity in the medial frontal cortex and posterior parietal cortex during an SWM task may be a neural correlate of increased vulnerability to psychosis.

The neural correlates of fatigue: an exploratory imaginal fatigue provocation study in chronic fatigue syndrome.

BACKGROUND: Fatigue is the central symptom in chronic fatigue syndrome (CFS) and yet very little is known about its neural correlates. The aim of this study was to explore the functional brain response, using functional magnetic resonance imaging (fMRI), to the imaginal experience of fatigue in CFS patients and controls. METHOD: We compared the blood oxygen level dependent (BOLD) responses of 12 CFS patients and 11 healthy controls to a novel fatigue provocation procedure designed to mimic real-life situations. A non-fatiguing anxiety-provoking condition was also included to control for the non-specific effects of negative affect. RESULTS: During the provocation of fatigue, CFS patients reported feelings of both fatigue and anxiety and, compared to controls, they showed increased activation in the occipito-parietal cortex, posterior cingulate gyrus and parahippocampal gyrus, and decreased activation in dorsolateral and dorsomedial prefrontal cortices. The reverse pattern of findings was observed during the anxiety-provoking scenarios. CONCLUSIONS: The results may suggest that, in CFS patients, the provocation of fatigue is associated with exaggerated emotional responses that patients may have difficulty suppressing. These findings are discussed in relation to the cognitive-behavioural model of CFS.

Neural responses to dynamic expressions of fear in schizophrenia.

Abnormalities in social functioning are a significant feature of schizophrenia. One critical aspect of these abnormalities is the difficulty these individuals have with the recognition of facial emotions, particularly negative expressions such as fear. The present work focuses on fear perception and its relationship to the paranoid symptoms of schizophrenia, specifically, how underlying limbic system structures (i.e. the amygdala) react when probed with dynamic fearful facial expressions. Seven paranoid and eight non-paranoid subjects (all males) with a diagnosis of schizophrenia took part in functional magnetic resonance imaging study (1.5T) examining neural responses to emerging fearful expressions contrasted with dissipating fearful expressions. Subjects viewed emerging and dissipating expressions while completing a gender discrimination task. Their brain activation was compared to that of 10 healthy male subjects. Increased hippocampal activation was seen in the non-paranoid group, while abnormalities in the bilateral amygdalae were observed only in the paranoid individuals. These patterns may represent trait-related hippocampal dysfunction, coupled with state (specifically paranoia) related amygdala abnormalities. The findings are discussed in light of models of paranoia in schizophrenia.

Personality factors correlate with regional cerebral perfusion.

There is an increasing body of evidence pointing to a neurobiological basis of personality. The purpose of this study was to investigate the biological bases of the major dimensions of Eysenck's and Cloninger's models of personality using a noninvasive magnetic resonance perfusion imaging technique in 30 young, healthy subjects. An unbiased voxel-based analysis was used to identify regions where the regional perfusion demonstrated significant correlation with any of the personality dimensions. Highly significant positive correlations emerged between extraversion and perfusion in the basal ganglia, thalamus, inferior frontal gyrus and cerebellum and between novelty seeking and perfusion in the cerebellum, cuneus and thalamus. Strong negative correlations emerged between psychoticism and perfusion in the basal ganglia and thalamus and between harm avoidance and perfusion in the cerebellar vermis, cuneus and inferior frontal gyrus. These observations suggest that personality traits are strongly associated with resting cerebral perfusion in a variety of cortical and subcortical regions and provide further evidence for the hypothesized neurobiological basis of personality. These results may also have important implications for functional neuroimaging studies, which typically rely on the modulation of cerebral hemodynamics for detection of task-induced activation since personality effects may influence the intersubject variability for both task-related activity and resting cerebral perfusion. This technique also offers a novel approach for the exploration of the neurobiological correlates of human personality.

Plasma level-dependent effects of methylphenidate on task-related functional magnetic resonance imaging signal changes.

RATIONALE: Methylphenidate (MPH) is a dopamine and noradrenaline enhancing drug used to treat attentional deficits. Understanding of its cognition-enhancing effects and the neurobiological mechanisms involved, especially in elderly people, is currently incomplete. OBJECTIVES: The aim of this study was to investigate the relationship between MPH plasma levels and brain activation during visuospatial attention and movement preparation. METHODS: Twelve healthy elderly volunteers were scanned twice using functional magnetic resonance imaging (fMRI) after oral administration of MPH 20 mg or placebo in a within-subject design. The cognitive paradigm was a four-choice reaction time task presented at two levels of difficulty (with and without spatial cue). Plasma MPH levels were measured at six time points between 30 and 205 min after dosing. FMRI data were analysed using a linear model to estimate physiological response to the task and nonparametric permutation tests for inference. RESULTS: Lateral premotor and medial posterior parietal cortical activation was increased by MPH, on average, over both levels of task difficulty. There was considerable intersubject variability in the pharmacokinetics of MPH. Greater area under the plasma concentration-time curve was positively correlated with strength of activation in motor and premotor cortex, temporoparietal cortex and caudate nucleus during the difficult version of the task. CONCLUSION: This is the first pharmacokinetic/pharmacodynamic study to find an association between plasma levels of MPH and its modulatory effects on brain activation measured using fMRI. The results suggest that catecholaminergic mechanisms may be important in brain adaptivity to task difficulty and in task-specific recruitment of spatial attention systems.

Dopaminergic drug effects on physiological connectivity in a human cortico-striato-thalamic system.

Cortico-striato-thalamic (CST) systems are anatomical substrates for many motor and executive functions and are implicated in diverse neuropsychiatric disorders. Electrophysiological studies in rats, monkeys and patients with Parkinson's disease have shown that power and coherence of low frequency oscillations in CST systems can be profoundly modulated by dopaminergic drugs. We combined functional MRI with correlational and path analyses to investigate functional and effective connectivity, respectively, of a prefronto-striato-thalamic system activated by object location learning in healthy elderly human subjects (n = 23; mean age = 72 years). Participants were scanned in a repeated measures, randomized, placebo-controlled design to measure modulation of physiological connectivity between CST regions following treatment with drugs which served both to decrease (sulpiride) and increase (methylphenidate) dopaminergic transmission, as well as non-dopaminergic treatments (diazepam and scopolamine) to examine non-specific effects. Functional connectivity of caudate nucleus was modulated specifically by dopaminergic drugs, with opposing effects of sulpiride and methylphenidate. The more salient effect of sulpiride was to increase functional connectivity between caudate and both thalamus and ventral midbrain. A path diagram based on prior knowledge of unidirectional anatomical projections between CST components was fitted satisfactorily to the observed inter-regional covariance matrix. The effect of sulpiride was defined more specifically in the context of this model as increased strength of effective connection from ventral midbrain to caudate nucleus. In short, we have demonstrated enhanced functional and effective connectivity of human caudate nucleus following sulpiride treatment, which is compatible both with the anatomy of ascending dopaminergic projections and with electrophysiological studies indicating abnormal coherent oscillations of CST neurons in parkinsonian states.