Pregenual Anterior Cingulate Cortex Research Articles

Positive Allosteric Modulator of GABA Lowers BOLD Responses in the Cingulate Cortex.

Knowledge about the neural underpinnings of the negative blood oxygen level dependent (BOLD) responses in functional magnetic resonance imaging (fMRI) is still limited. We hypothesized that pharmacological GABAergic modulation attenuates BOLD responses, and that blood concentrations of a positive allosteric modulator of GABA correlate inversely with BOLD responses in the cingulate cortex. We investigated whether or not pure task-related negative BOLD responses were co-localized with pharmacologically modulated BOLD responses. Twenty healthy adults received either 5 mg diazepam or placebo in a double blind, randomized design. During fMRI the subjects performed a working memory task. Results showed that BOLD responses in the cingulate cortex were inversely correlated with diazepam blood concentrations; that is, the higher the blood diazepam concentration, the lower the BOLD response. This inverse correlation was most pronounced in the pregenual anterior cingulate cortex and the anterior mid-cingulate cortex. For subjects with diazepam plasma concentration > 0.1 mg/L we observed negative BOLD responses with respect to fixation baseline. There was minor overlap between cingulate regions with task-related negative BOLD responses and regions where the BOLD responses were inversely correlated with diazepam concentration. We interpret that the inverse correlation between the BOLD response and diazepam was caused by GABA-related neural inhibition. Thus, this study supports the hypothesis that GABA attenuates BOLD responses in fMRI. The minimal overlap between task-related negative BOLD responses and responses attenuated by diazepam suggests that these responses might be caused by different mechanisms.

Anhedonic brain while attending sexual and emotional pictures

Anhedonia is defined as the inability to gain pleasure from normally pleasurable experiences and reduced sexual desire. Rees et al. (2007) showed that limbic and paralimbic areas are responsible for sexual arousal and that anhedonia is associated with frontolimbic inhibition. In major depression, reduced ventral striatum and increased ventral prefrontal cortex areas was associated with anhedonia(Gorwood, 2009). Walter et al. (2009) indicated that there is a deviation in the neuronal activation pattern of the pregenual anterior cingulate cortex in anhedonic depression which is related to a glutamergic deficit. Glutamate was suggested to play a relevant role in reward system (Birgner et al., 2005). ACC is a key involved in affective state and glutamate mediates ACC activation to sexual attraction(Wu et al., 2009). Thus, a glutamatergic deficit might be related to reduced hedonic effect specific to major depression. Using an attention modulation of emotional and sexual pictures, we investigate the role of anhedonia on the ventral and dorsal systems in healthy volunteers and patients with major depression. They undergo an expectancy task in a 7 T scanner and passively view sexual and emotional photographs and are asked to expect either high salient pictures or high erotic pictures. Half of these pictures are announced by an expectancy cue, whereas the other half are preceded by a fixation cross. Snaith-Hamilton-Pleasure-Scale and Hamilton Depression Rating Scale are employed to assess anhedonia and depressive symptom severity. Brain metabolites in the dorsal and pgACC are measured using MRS. We will show how anhedonia modulates the neural response to sexual arousal.Disclosure of interestThe author has not supplied his/her declaration of competing interest.

Ketamine administration reduces amygdalo-hippocampal reactivity to emotional stimulation.

Increased amygdala reactivity might lead to negative bias during emotional processing that can be reversed by antidepressant drug treatment. However, little is known on how N-methyl-d-aspartate (NMDA) receptor antagonism with ketamine as a novel antidepressant drug target might modulate amygdala reactivity to emotional stimulation. Using functional magnetic resonance imaging (fMRI) and resting-state fMRI (rsfMRI), we assessed amygdalo-hippocampal reactivity at baseline and during pharmacological stimulation with ketamine (intravenous bolus of 0.12 mg/kg, followed by a continuous infusion of 0.25 mg/kg/h) in 23 healthy subjects that were presented with stimuli from the International Affective Picture System (IAPS). We found that ketamine reduced neural reactivity in the bilateral amygdalo-hippocampal complex during emotional stimulation. Reduced amygdala reactivity to negative pictures was correlated to resting-state connectivity to the pregenual anterior cingulate cortex. Interestingly, subjects experienced intensity of psychedelic alterations of consciousness during ketamine infusion predicted the reduction in neural responsivity to negative but not to positive or neutral stimuli. Our findings suggest that the pharmacological modulation of glutamate-responsive cerebral circuits, which is associated with a shift in emotional bias and a reduction of amygdalo-hippocampal reactivity to emotional stimuli, represents an early biomechanism to restore parts of the disrupted neurobehavioral homeostasis in MDD patients. Hum Brain Mapp 37:1941-1952, 2016. © 2016 Wiley Periodicals, Inc.

Psychosurgery Reduces Uncertainty and Increases Free Will? A Review.

A definition of free will is the ability to select for or against a course of action to fulfill a desire, without extrinsic or intrinsic constraints that compel the choice. Free will has been linked to the evolutionary development of flexible decision making. In order to develop flexibility in thoughts and behavioral responses, learning mechanisms have evolved as a modification of reflexive behavioral strategies. The ultimate goal of the brain is to reduce uncertainty inherently present in a changing environment. A way to reduce the uncertainty, which is encoded by the rostral anterior cingulate, is to make multiple predictions about the environment which are updated in parallel by sensory inputs. The prediction/behavioral strategy that fits the sensory input best is then selected, becomes the next percept/behavioral strategy, and is stored as a basis for future predictions. Acceptance of predictions (positive feedback) is mediated via the accumbens, and switching to other predictions by the dorsal anterior cingulate cortex (ACC) (negative feedback). Maintenance of a prediction is encoded by the pregenual ACC. Different cingulate territories are involved in rejection, acceptance and maintenance of predictions. Free will is known to be decreased in multiple psychopathologies, including obsessive compulsive disorder and addictions. In modern psychosurgery three target structures exist for obsessive compulsive disorder and addiction: the dorsal ACC, the nucleus accumbens, and/or the anterior limb of the internal capsula. Research in all three areas reports favorable results with acceptable side effects. Psychosurgical interventions seem to exert their effect by a common final common pathway mediated via the pregenual ACC. Successful neuromodulation increases the capacity to choose from different options for the affected individual, as well as inhibiting unwanted options, therefore increasing free will and free won't.

Brain Areas Involved in Anticipation of Clinically Relevant Pain in Low Back Pain Populations With High Levels of Pain Behavior.

The purpose of this study was to identify neural correlates of pain anticipation in people with nonspecific low back pain (NSLBP) that correlated with pain-related distress and disability, thus providing evidence for mechanisms underlying pain behavior in this population. Thirty NSLBP sufferers, with either high levels of pain behavior or low levels on the basis of Waddell signs, were scanned with functional magnetic resonance imaging while a straight-leg raise (of the side deemed to cause moderate pain in the lower back) was performed. On each trial colored stimuli were presented and used to indicate when the leg definitely would be raised (green; 100% certainty), might be raised (yellow; 50% certainty), or would definitely not be raised (red; 100% certainty). In response to expected versus unexpected pain the group difference in activation between patients with high levels of pain behavior and low levels of pain behavior covaried as a function of anxiety scores in the right insula and pregenual anterior cingulate cortex and as a function of catastrophizing in prefrontal and parietal cortex and hippocampus. The results suggest NSLBP populations with the highest levels of pain-related distress are more likely to attend to and infer threat from innocuous cues, which may contribute to the maintenance of pain behavior associated with some chronic pain states. This article shows a likely neural network for exacerbating pain anticipation in NSLBP contributing to high levels of pain behavior in some people. This information could potentially help clinicians and patients to understand how anticipation of pain may contribute to patient pain and disability.

State and Training Effects of Mindfulness Meditation on Brain Networks Reflect Neuronal Mechanisms of Its Antidepressant Effect.

The topic of investigating how mindfulness meditation training can have antidepressant effects via plastic changes in both resting state and meditation state brain activity is important in the rapidly emerging field of neuroplasticity. In the present study, we used a longitudinal design investigating resting state fMRI both before and after 40 days of meditation training in 13 novices. After training, we compared differences in network connectivity between rest and meditation using common resting state functional connectivity methods. Interregional methods were paired with local measures such as Regional Homogeneity. As expected, significant differences in functional connectivity both between states (rest versus meditation) and between time points (before versus after training) were observed. During meditation, the internal consistency in the precuneus and the temporoparietal junction increased, while the internal consistency of frontal brain regions decreased. A follow-up analysis of regional connectivity of the dorsal anterior cingulate cortex further revealed reduced connectivity with anterior insula during meditation. After meditation training, reduced resting state functional connectivity between the pregenual anterior cingulate and dorsal medical prefrontal cortex was observed. Most importantly, significantly reduced depression/anxiety scores were observed after training. Hence, these findings suggest that mindfulness meditation might be of therapeutic use by inducing plasticity related network changes altering the neuronal basis of affective disorders such as depression.

Association between resting-state brain functional connectivity and muscle sympathetic burst incidence.

The insula (IC) and cingulate are key components of the central autonomic network and central nodes of the salience network (SN), a set of spatially distinct but temporally correlated brain regions identified with resting-state (task free) functional MRI (rsMRI). To examine the SN's involvement in sympathetic outflow, we tested the hypothesis that individual differences in intrinsic connectivity of the SN correlate positively with resting postganglionic muscle sympathetic nerve activity (MSNA) burst incidence (BI) in subjects without and with obstructive sleep apnea (OSA). Overnight polysomnography, 5-min rsMRI, and fibular MSNA recording were performed in 36 subjects (mean age 57 yr; 10 women, 26 men). Independent component analysis (ICA) of the entire cohort identified the SN as including bilateral IC, pregenual anterior cingulate cortex (pgACC), midcingulate cortex (MCC), and the temporoparietal junction (TPJ). There was a positive correlation between BI and the apnea-hypopnea index (AHI) (P < 0.001), but dual-regression analysis identified no differences in SN functional connectivity between subjects with no or mild OSA (n = 17) and moderate or severe (n = 19) OSA. Correlation analysis relating BI to the strength of connectivity within the SN revealed large (i.e., spatial extent) and strong correlations for the left IC (P < 0.001), right pgACC/MCC (P < 0.006), left TPJ (P < 0.004), thalamus (P < 0.035), and cerebellum (P < 0.013). Indexes of sleep apnea were unrelated to BI and the strength of SN connectivity. There were no relationships between BI and default or sensorimotor network connectivity. This study links connectivity within the SN to MSNA, demonstrating several of its nodes to be key sympathoexcitatory regions.

Subclinical depression severity is associated with distinct patterns of functional connectivity for subregions of anterior cingulate cortex

Depression is a prevalent psychiatric condition characterized by sad mood and anhedonia. Neuroscientific research has consistently identified abnormalities in a network of brain regions in major depression, including subregions of the anterior cingulate cortex (ACC). However, few studies have investigated whether the same neural correlates of depression symptom severity are apparent in subclinical or healthy subjects. In the current study, we used resting-state fMRI to examine functional connectivity for subregions of the ACC in N = 28 participants with subclinical levels of depression. In regression analyses, we examined relationships between depression severity and functional connectivity for pregenual ACC (pgACC), anterior subgenual ACC (sgACC), and posterior sgACC seed regions. Additionally, we examined relationships between ACC subregion connectivity and trait levels of positive and negative affect. We found distinct associations between depression severity and functional connectivity of ACC subregions. Higher depression severity was associated with reduced pgACC-striatum connectivity and reduced anterior sgACC-anterior insula connectivity. Consistent with resting-state findings in major depression, higher depression severity was also related to greater anterior sgACC-posterior cingulate connectivity and greater posterior sgACC-dorsolateral prefrontal connectivity. Lastly, there were distinct correlations between connectivity for anterior versus posterior ACC subregions and positive and negative affective traits. These findings provide novel support linking subclinical depression to the same neural substrates associated with major depression. More broadly, these results contribute to an emerging literature on dimensional approaches to psychiatric illness.

Effects of acute tryptophan depletion on raphé functional connectivity in depression

Depression remains a great societal burden and a major treatment challenge. Most antidepressant medications target serotonergic raphé nuclei. Acute tryptophan depletion (ATD) modulates serotonin function. To better understand the raphé's role in mood networks, we studied raphé functional connectivity in depression. Fifteen depressed patients were treated with sertraline for 12 weeks and scanned during ATD and sham conditions. Based on our previous findings in a separate cohort, resting state MRI functional connectivity between raphé and other depression-related regions (ROIs) was analyzed in narrow frequency bands. ATD decreased raphé functional connectivity with the bilateral thalamus within 0.025–0.05Hz, and also decreased raphé functional connectivity with the right pregenual anterior cingulate cortex within 0.05–0.1Hz. Using the control broadband filter 0.01–0.1Hz, no significant differences in raphé-ROI functional connectivity were observed. Post-hoc analysis by remission status suggested increased raphé functional connectivity with left pregenual anterior cingulate cortex in remitters (n=10) and decreased raphé functional connectivity with left thalamus in non-remitters (n=5), both within 0.025–0.05Hz. Reducing serotonin function appears to alter coordination of these mood-related networks in specific, low frequency ranges. For examination of effects of reduced serotonin function on mood-related networks, specific low frequency BOLD fMRI signals can identify regions implicated in neural circuitry and may enable clinically-relevant interpretation of functional connectivity measures. The biological significance of these low frequency signals detected in the raphé merits further study.

Metabolic mapping reveals sex-dependent involvement of default mode and salience network in alexithymia.

Alexithymia, a personality construct marked by difficulties in processing one's emotions, has been linked to the altered activity in the anterior cingulate cortex (ACC). Although longitudinal studies reported sex differences in alexithymia, what mediates them is not known. To investigate sex-specific associations of alexithymia and neuronal markers, we mapped metabolites in four brain regions involved differentially in emotion processing using a point-resolved spectroscopy MRS sequence in 3 Tesla. Both sexes showed negative correlations between alexithymia and N-acetylaspartate (NAA) in pregenual ACC (pgACC). Women showed a robust negative correlation of the joint measure of glutamate and glutamine (Glx) to NAA in posterior cingulate cortex (PCC), whereas men showed a weak positive association of Glx to NAA in dorsal ACC (dACC). Our results suggest that lowered neuronal integrity in pgACC, a region of the default mode network (DMN), might primarily account for the general difficulties in emotional processing in alexithymia. Association of alexithymia in women extends to another region in the DMN-PCC, while in men a region in the salience network (SN) was involved. These observations could be representative of sex specific regulation strategies that include diminished internal evaluation of feelings in women and cognitive emotion suppression in men.

Neural Correlates of Empathy with Pain Show Habituation Effects. An fMRI Study.

BackgroundNeuroimaging studies have demonstrated that the actual experience of pain and the perception of another person in pain share common neural substrates, including the bilateral anterior insular cortex and the anterior midcingulate cortex. As many fMRI studies include the exposure of participants to repeated, similar stimuli, we examined whether empathic neural responses were affected by habituation and whether the participants' prior pain experience influenced these habituation effects.MethodIn 128 trials (four runs), 62 participants (31 women, 23.0 ± 4.2 years) were shown pictures of hands exposed to painful pressure (pain pictures) and unexposed (neutral pictures). After each trial, the participants rated the pain of the model. Prior to the experiment, participants were either exposed to the same pain stimulus (pain exposure group) or not (touch exposure group). In order to assess possible habituation effects, linear changes in the strength of the BOLD response to the pain pictures (relative to the neutral pictures) and in the ratings of the model’s pain were evaluated across the four runs.ResultsAlthough the ratings of the model’s pain remained constant over time, we found neural habituation in the bilateral anterior/midinsular cortex, the posterior midcingulate extending to dorsal posterior cingulate cortex, the supplementary motor area, the cerebellum, the right inferior parietal lobule, and the left superior frontal gyrus, stretching to the pregenual anterior cingulate cortex. The participant’s prior pain experience did neither affect their ratings of the model’s pain nor their maintenance of BOLD activity in areas associated with empathy. Interestingly, participants with high trait personal distress and fantasy tended to show less habituation in the anterior insula.ConclusionNeural structures showed a decrease of the BOLD signal, indicating habituation over the course of 45 minutes. This can be interpreted as a neuronal mechanism responding to the repeated exposure to pain depictions, which may be regarded as functional in a range of contexts.

Voxel Based Morphometry Alterations in Mal de Debarquement Syndrome.

BackgroundMal de debarquement syndrome (MdDS) is a disorder of chronic self-motion perception that occurs though entrainment to rhythmic background motion, such as from sea voyage, and involves the perception of low-frequency rocking that can last for months or years. The neural basis of this persistent sensory perception abnormality is not well understood.MethodsWe investigated grey matter volume differences underlying persistent MdDS by performing voxel-based morphometry on whole brain and pre-specified ROIs in 28 individuals with MdDS and comparing them to 18 age, sex, and handedness matched controls.ResultsMdDS participants exhibited greater grey matter volume in the left inferior parietal lobule, right inferior occipital gyrus (area V3v), right temporal pole, bilateral cerebellar hemispheric lobules VIII/IX and left lobule VIIa/VIIb. Grey matter volumes were lower in bilateral inferior frontal, orbitofrontal, pregenual anterior cingulate cortex (pgACC) and left superior medial gyri (t = 3.0, p<0.005uncorr). In ROI analyses, there were no volume differences in the middle occipital gyrus (region of V5/MT) or parietal operculum 2 (region of the parietoinsular vestibular cortex). Illness duration was positively related to grey matter volume in bilateral inferior frontal gyrus/anterior insula (IFG/AI), right posterior insula, superior parietal lobule, left middle occipital gyrus (V5/MT), bilateral postcentral gyrus, anterior cerebellum, and left cerebellar hemisphere and vermian lobule IX. In contrast, illness duration was negatively related to volume in pgACC, posterior middle cingulate gyrus (MCC), left middle frontal gyrus (dorsolateral prefrontal cortex-DLPFC), and right cerebellar hemispheric lobule VIIIb (t = 3.0, p<0.005uncorr). The most significant differences were decreased volume in the pgACC and increased volume in the left IFG/AI with longer illness duration (qFDRcorr <0.05). Concurrent medication use did not correlate with these findings or have a relationship with duration of illness. MdDS participants showed positive correlations between grey matter volume in pgACC and bilateral cerebellar lobules VIII/IX, which was not seen in controls.ConclusionsIndividuals with MdDS show brain volume differences from healthy controls as well as duration of illness dependent volume changes in (a) visual-vestibular processing areas (IPL, SPL, V3, V5/MT), (b) default mode network structures (cerebellar IX, IPL, ACC), (c) salience network structures (ACC and IFG/AI) (d) somatosensory network structures (postcentral gyrus, MCC, anterior cerebellum, cerebellar lobule VIII), and (e) a structure within the central executive network (DLPFC). The identification of these associations may enhance future investigations into how exposure to oscillating environments can modulate brain function and affect motion perception as well cognitive and affective control.

Mirth and laughter elicited by electrical stimulation of the human anterior cingulate cortex

Laughter is a complex motor behavior that, typically, expresses mirth. Despite its fundamental role in social life, knowledge about the neural basis of laughter is very limited and mostly based on a few electrical stimulation (ES) studies carried out in epileptic patients. In these studies laughter was elicited from temporal areas where it was accompanied by mirth and from frontal areas plus an anterior cingulate case where laughter without mirth was observed. On the basis of these findings, it has been proposed a dichotomy between temporal lobe areas processing the emotional content of laughter and anterior cingulate cortex (ACC) and motor areas responsible of laughter production. The present study is aimed to understand the role of ACC in laughter. We report the effects of stimulation of 10 rostral, pregenual ACC (pACC) patients in which the ES elicited laughter. In half of the patients ES elicited a clear burst of laughter with mirth, while in the other half mirth was not evident. This large dataset allow us to offer a more reliable picture of the functional contribute of this region in laughter, and to precisely localize it in the cingulate cortex. We conclude that the pACC is involved in both the motor and the affective components of emotions, and challenge the validity of a sharp dichotomy between motor and emotional centers for laughing. Finally, we suggest a possible anatomical network for the production of positive emotional expressions.

Frequency-Specific Alterations of Local Synchronization in Idiopathic Generalized Epilepsy.

Recurrently and abnormally hypersynchronous discharge is a striking feature of idiopathic generalized epilepsy (IGE). Resting-state functional magnetic resonance imaging has revealed aberrant spontaneous brain synchronization, predominately in low-frequency range (<0.1 Hz), in individuals with IGE. Little is known, however, about these changes in local synchronization across different frequency bands. We examined alterations to frequency-specific local synchronization in terms of spontaneous blood oxygen level-dependent (BOLD) fluctuations across 5 bands, spanning 0 to 0.25 Hz. Specifically, we compared brain activity in a large cohort of IGE patients (n = 86) to age- and sex-matched normal controls (n = 86). IGE patients showed decreased local synchronization in low frequency (<0.073 Hz), primarily in the default mode network (DMN). IGE patients also exhibited increased local synchronization in high-frequency (>0.073 Hz) in a "conscious perception network," which is anchored by the pregenual and dorsal anterior cingulate cortex, as well as the bilateral insular cortices, possibly contributing to impaired consciousness. Furthermore, we found frequency-specific alternating local synchronization in the posterior portion of the DMN relative to the anterior part, suggesting an interaction between the disease and frequency bands. Importantly, the aberrant high-frequency local synchronization in the middle cingulate cortex was associated with disease duration, thus linking BOLD frequency changes to disease severity. These findings provide an overview of frequency-specific local synchronization of BOLD fluctuations, and may be helpful in uncovering abnormal synchronous neuronal activity in patients with IGE at specific frequency bands.

Fear avoidance beliefs in back pain-free subjects are reflected by amygdala-cingulate responses.

In most individuals suffering from chronic low back pain, psychosocial factors, specifically fear avoidance beliefs (FABs), play central roles in the absence of identifiable organic pathology. On a neurobiological level, encouraging research has shown brain system correlates of somatic and psychological factors during the transition from (sub) acute to chronic low back pain. The characterization of brain imaging signatures in pain-free individuals before any injury will be of high importance regarding the identification of relevant networks for low back pain (LBP) vulnerability. Fear-avoidance beliefs serve as strong predictors of disability and chronification in LBP and current research indicates that back pain related FABs already exist in the general and pain-free population. Therefore, we aimed at investigating possible differential neural functioning between high- and low fear-avoidant individuals in the general population using functional magnetic resonance imaging. Results revealed that pain-free individuals without a history of chronic pain episodes could be differentiated in amygdala activity and connectivity to the pregenual anterior cingulate cortex by their level of back pain related FABs. These results shed new light on brain networks underlying psychological factors that may become relevant for enhanced disability in a future LBP episode.

Methadone maintenance dose modulates anterior cingulate glutamate levels in heroin-dependent individuals: A preliminary in vivo1H MRS study

Mu-opioid receptor agonists alter brain glutamate (GLU) levels in laboratory animals. This clinical study used proton magnetic resonance spectroscopy (1H MRS) to examine regional brain GLU levels during experimental manipulation of methadone (MTD) maintenance dose under double-blind, within-subject conditions in seven heroin-dependent volunteers. Subjects were scanned first at a high MTD dose (100mg/day), underwent a 3-week outpatient MTD dose taper, and then were scanned again at a low MTD dose (10–25mg/day; modified for participant comfort). Five age- and cigarette smoking-matched controls were scanned once. In vivo short echo time (TE=22ms), single voxel 1H MRS data from midline pregenual anterior cingulate cortex (ACC) and thalamus (4.5cm3 each) were collected using PRESS on a 4-Tesla MRI system. Absolute metabolite levels were quantified. GLU levels in the ACC, but not the thalamus, were higher at the low relative to the high MTD dose in heroin-dependent subjects. No other metabolites differed by MTD dose, or between control vs. heroin-dependent subjects (at either MTD dose). GLU levels in the ACC were inversely related to the duration of cigarette smoking (controls) and heroin use (experimental group). Future studies are warranted to investigate the relationship between GLU levels during treatment (and detoxification), and withdrawal symptoms or relapse.

Quantification of N-Acetyl Aspartyl Glutamate in Human Brain using Proton Magnetic Resonance Spectroscopy at 7 T

UDC 543.422.25:611.81 The separation of N-acetyl aspartyl glutamate (NAAG) from N-acetyl aspartate (NAA) and other metabolites, such as glutamate, by in vivo proton magnetic resonance spectroscopy at 7 T is described. This method is based on the stimulated echo acquisition mode (STEAM), with short and long echo time (TE) and allows quantitative measurements of NAAG in the parietal and pregenual anterior cingulate cortex (pgACC) of human brain. Two base- sets for the LCModel have been established using nuclear magnetic resonance simulator software (NMR-SIM). Six healthy volunteers (age 25-35 years) have been examined at 7 T. It has been established that NAAG can be separated and quantifi ed in the parietal location and does not get quantifi ed in the pgACC location when using a short echo time, TE = 20 ms. On the other hand, by using a long echo time, TE = 74 ms, NAAG can be quantifi ed in pgACC structures. LCModel. Introduction. N-Acetylaspartylglutamic acid (NAAG) is a neuropeptide that is the third most prevalent neurotransmitter in the human brain (1). NAAG is produced by the coupling between a glutamic acid (Glu) and the N-acetylaspartic acid (NAA) via a peptide bond. Therefore, it may be diffi cult to distinguish between them on account of the similarity of the chemical structure. In human studies, it has been suggested that NAAG levels are abnormal in patients with schizophrenia (2) and decreased in amyotrophic lateral sclerosis (ALS) (3). In a previous study (4), it had been diffi cult to distinguish NAAG from NAA and Glu using proton magnetic resonance spectroscopy (MRS) at 3 T. As the dominant signal of the NAAG spectrum from the N-acetyl proton resonance peak is located at 2.05 ppm, which is 0.03 ppm away from the corresponding NAA signal at 2.02 ppm (5), a high resolution of metabolite peaks can be obtained using ultrahigh-fi eld strengths such as 7 T (6, 7) or at high fi elds (2 or 3 T), with unusual shimming (8). Proton magnetic resonance spectroscopy provides markers for various human brain diseases (9, 10). Some of the important measurement characteristics of the MRS technique are the signal-to-noise ratio (SNR), spatial and spectral resolution, as well as scan time; thus, several localization methods have been proposed. Single volume spectroscopy (SVS) localization techniques, with pulse sequences based on spin echoes (PRESS) (11) or stimulated echoes (STEAM) (12), provide the highest spectral quality (13), as the lower magnetic fi eld strengths result in a peak overlap of the human brain metabolites, such as, NAA with NAAG. Besides, standard spectroscopic sequences such as STEAM or PRESS will suffer if limited transmitter voltage takes place. This results in a reduced excitation flip angle and consequently insuffi cient excitation in the volume of interest (VOI). Moreover, previous studies have shown that the increase in magnetic field strength increases the 1 H NMR spectral peak separation and SNR and thus provides higher sensitivity when compared with lower field strengths (14, 15). With standard radio-frequency (RF) amplifiers and volume RF coils at 7 T, short 180° refocusing pulses are diffi cult to achieve in most parts of the brain. Therefore, earlier, high field MRS studies frequently employed surface coils with locally higher RF fi eld amplitude (16, 17). However, not all brain areas can be adequately examined using surface coils. As the goal of this study is to quantify the NAAG concentrations in different brain structures, STEAM with short echo time benefits, from reduced signal decay, because of the J-evolution of the coupled spin system, allows a more precise quantification of the metabolites, especially with a short T2 relaxation time (18). Thus, short echo times have been used in several studies (19). In the current study, echo time (TE) was selected to be short and long 20 and 74 ms, respectively. Although earlier studies had employed STEAM with ultrashort echo times (6 ms), they were limited by the surface coils that prevented detection in the deep brain regions (20). Also, a quadrature (transmit/receive) surface RF coil or a half-volume RF coil have been used for the

Resting-state fMRI study on brain network in depression

Objective Depression is a mood disorder that causes a persistent feeling of sadness, with high morbidity rates and great social impairment. Increasingly studies show the abnormalities of brain networks. We summarized the results of functional magnetic resonance imaging study of depression, and demonstrated the neural loops mechanism from neuroimaing perspective. Methods The key words , resting state and were searched in PubMed, CNKI and Wan Fang databases from January 2000 to December 2014. The nodes of depression related network and the alterations of cortex resting-state networks were summarized. Results 24 studies focusing on network of depression were identified. 40 studies based on ROI (region of interest) analysis, which included amygdala, frontal lobe, pregenual anterior cingulate cortex and cerebellum. The functional connectivity of ROIs were calculated and compared between groups. 8 studies based on ICA (independent component analysis), the networks were extracted and compared between groups. Two based on graph theory, the functional connectivity of whole brain were analyzed and compared. Conclusion There are abnormalities of functional connectivity among limbic system-thalamus-frontal cortex, and the changes of functional connectivity were associated with clinical symptom and drug efficacy of depression. Key words: Depression, resting-state fMRI; Brain network

Altered functional connectivity of the cingulate subregions in schizophrenia.

Schizophrenia patients have shown altered resting-state functional connectivity (rsFC) of the cingulate cortex; however, it is unknown whether rsFCs of the cingulate subregions are differentially affected in this disorder. We aimed to clarify the issue by comparing rsFCs of each cingulate subregion between healthy controls and schizophrenia patients. A total of 102 healthy controls and 94 schizophrenia patients underwent resting-state functional magnetic resonance imaging with a sensitivity-encoded spiral-in imaging sequence to reduce susceptibility-induced signal loss and distortion. The cingulate cortex was divided into nine subregions, including the subgenual anterior cingulate cortex (ACC), areas 24 and 32 of the pregenual ACC, areas 24 and 32 of the anterior mid-cingulate cortex (aMCC), posterior MCC (pMCC), dorsal (dPCC) and ventral (vPCC) posterior cingulate cortex (PCC) and retrosplenial cortex (RSC). The rsFCs of each cingulate subregion were compared between the two groups and the atrophy effect was considered. Results with and without global signal regression were reported. Most cingulate subregions exhibited decreased rsFCs in schizophrenia after global signal regression (GSR). Without GSR, only increased rsFC was found in schizophrenia, which primarily restricted to the aMCC, PCC and RSC. Some of these increased rsFCs were also significant after GSR. These findings suggest that GSR can greatly affect between-group differences in rsFCs and the consistently increased rsFCs may challenge the functional disconnection hypothesis of schizophrenia.

Actor-recipient role affects neural responses to self in emotional situations.

People often take either the role of an actor or that of recipient in positive and negative interpersonal events when they interact with others. The present study investigated how the actor-recipient role affected the neural responses to self in emotional situations. Twenty-five participants were scanned while they were presented with positive and negative interpersonal events and were asked to rate the degree to which the actor/the recipient was that kind of person who caused the interpersonal event. Half of the trials were self-relevant events and the other half were other-relevant events. Results showed that people were more likely to isolate self from negative events when they played the role of actor relative to recipient. Pregenual anterior cingulate cortex (pgACC) and posterior dorsal anterior cingulate cortex (pdACC) were more active for self than other only in negative events. More importantly, also in negative interpersonal events, dorsal medial prefrontal cortex (dmPFC) showed greater self-related activations (self-other) when participants played the role of recipient relative to actor, while activities in orbitofrontal cortex (OFC) were greater for self than other only when the evaluation target played the role of recipient. These results showed that the actor-recipient role affected neural responses to self in emotional situations, especially when a recipient role was played in negative situations.