Representing magnitude information in various dimensions, including space, quantity, and time, is an important function of the human brain. Many previous studies reported that numerical and spatial magnitudes could be mutually influenced through a "mental number line". In this study, we address the question of whether magnitudes in nontemporal dimensions and magnitudes in time are represented independently or not. Observers judged the duration of the stimuli while four types of nontemporal magnitude information, including number of dots, size of open squares, luminance of solid squares, and numeric value of digits, were manipulated in Stroop-like paradigms. Results revealed that stimuli with larger magnitudes in these nontemporal dimensions were judged to be temporally longer. This observation supports the idea that magnitudes in temporal and nontemporal dimensions are not independent and implies the existence of generalized and abstract components in the magnitude representations.

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Inflammation and altered glutamate metabolism are two pathways implicated in the pathophysiology of depression. Interestingly, these pathways may be linked given that administration of inflammatory cytokines such as interferon-α to otherwise non-depressed controls increased glutamate in the basal ganglia and dorsal anterior cingulate cortex (dACC) as measured by magnetic resonance spectroscopy (MRS). Whether increased inflammation is associated with increased glutamate among patients with major depression is unknown. Accordingly, we conducted a cross-sectional study of 50 medication-free, depressed outpatients using single-voxel MRS, to measure absolute glutamate concentrations in basal ganglia and dACC. Multivoxel chemical shift imaging (CSI) was used to explore creatine-normalized measures of other metabolites in basal ganglia. Plasma and cerebrospinal fluid (CSF) inflammatory markers were assessed along with anhedonia and psychomotor speed. Increased log plasma C-reactive protein (CRP) was significantly associated with increased log left basal ganglia glutamate controlling for age, sex, race, body mass index, smoking status and depression severity. In turn, log left basal ganglia glutamate was associated with anhedonia and psychomotor slowing measured by the finger-tapping test, simple reaction time task and the Digit Symbol Substitution Task. Plasma CRP was not associated with dACC glutamate. Plasma and CSF CRP were also associated with CSI measures of basal ganglia glutamate and the glial marker myoinositol. These data indicate that increased inflammation in major depression may lead to increased glutamate in the basal ganglia in association with glial dysfunction and suggest that therapeutic strategies targeting glutamate may be preferentially effective in depressed patients with increased inflammation as measured by CRP.

Cognitive impairments have been found in thyroid hormone-related diseases (e.g. hyperthyroidism and hypothyroidism) for a long time. However, whether and how subclinical hypothyroidism (SCH) causes any deficits in brain functions, and whether a hormone-replacement treatment is necessary for SCH patients, still remain controversial subjects. In the present study, functional MRI (fMRI) was used to measure brain functions by asking euthyroid subjects, hyperthyroid patients and SCH patients to perform the widely used digit n-back working memory task. After having been treated with l-thyroxine for approximately 6 months, the SCH patients were asked to do the same fMRI experiment. The hypothyroid and SCH patients scored significantly lower in the 2-back task than either the hyperthyroid patients or the euthyroid subjects (P < 0.012). The fMRI showed that a common frontoparietal network, including bilateral middle/inferior frontal gyri (M/IFG), bilateral dorsolateral prefrontal cortex (DLPFC), bilateral premotor areas (PreMA), the supplementary motor area/anterior cingulate cortex (SMA/ACC) and bilateral parietal areas (PA), was activated by the n-back task in all the subjects. Further quantitative analysis showed that the load effect of blood oxygen level-dependent (BOLD) response appeared in all the five regions of interest (ROIs) in the euthyroid and hyperthyroid subjects. In the pre-treatment SCH patients, however, the load effect of BOLD response was only found in the PA and PreMA, but not in other frontal cortex ROIs [general linear model (GLM), F < 2.6, P > 0.1]. After an approximately 6 month treatment with LT4, the SCH patients exhibited the same load effects in all five ROIs as the euthyroid subjects (GLM, F > 6, P < 0.05) along with an improvement of performance in n-back task. These results suggest that working memory (but not other memory functions) is impaired in SCH patients, mainly as far as disorders of the frontoparietal network were concerned. Both the memory performance and frontal executive functions were improved after an l-thyroxine-replacement treatment.

Cytokine effects on behavior may be related to alterations in glutamate metabolism. We therefore measured glutamate concentrations in brain regions shown to be affected by inflammatory stimuli including the cytokine interferon (IFN)-alpha. IFN-alpha is known to alter neural activity in the dorsal anterior cingulate cortex (dACC) and basal ganglia in association with symptoms of depression and increases in peripheral cytokines including the tumor necrosis factor (TNF) and its soluble receptor. Single-voxel magnetic resonance spectroscopy (MRS) was employed to measure glutamate concentrations normalized to creatine (Glu/Cr) in dACC and basal ganglia of 31 patients with hepatitis C before and after B1 month of either no treatment (n ¼ 14) or treatment with IFN-alpha (n ¼ 17). Depressive symptoms were measured at each visit using the Inventory of Depressive Symptoms-Clinician Rating (IDS-C) and the Multidimensional Fatigue Inventory. IFN-alpha was associated with a significant increase in Glu/Cr in dACC and left basal ganglia. Increases in dACC Glu/Cr were positively correlated with scores on the IDS-C in the group as a whole, but not in either group alone. Glu/Cr increases in left basal ganglia were correlated with decreased motivation in the group as a whole and in IFN-alpha-treated subjects alone. No Glu/Cr changes were found in the right basal ganglia, and no significant correlations were found between Glu/Cr and the inflammatory markers. IFN-alphainduced increases in glutamate in dACC and basal ganglia are consistent with MRS findings in bipolar depression and suggest that inflammatory cytokines may contribute to glutamate alterations in patients with mood disorders and increased inflammation.

We characterize the contrast behavior of substantia nigra (SN) in both magnetization transfer (MT) imaging, which is believed to be sensitive to neuromelanin (NM), and susceptibility weighted imaging (SWI). Images were acquired with a MT prepared dual echo gradient echo sequence. The first echo was taken as the MT contrast image and the second was used to generate the SWI image. SN volumes were segmented from these two types of images using a thresholding method. The spatial and signal characteristics of the extracted SWI and MT volumes were compared. Both images showed the presence of SN but the volumes of the SN identified in the two are spatially incongruent. The MT volume was more caudal than the SWI volume and with only a 12% overlap between the two volumes. Considering the SN volumes in each hemisphere separately, the average distances between the centers of mass of the volumes from the two types images are 5.1±1.1 mm and 4.1±1.2 mm, respectively. The frequency offsets (homodyne filtered phase/echo time) for the volumes derived from MT (NM) images and SWI images are 0.09±0.32 radians/s and -1.12±0.57 radians/s (p<0.0001), respectively. The MT contrasts for the two volumes are 0.16±0.02 and 0.10±0.03 (p<0.001), respectively. Our results indicate that the two contrasts are sensitive to different portions of the SN, with MT seeing the more caudal portion of the SN than SWI, likely due to variations of NM and iron content in the SN. Despite the small overlap, these regions are complementary. Our results provide a new understanding of the contrast behavior of the SN in the two imaging approaches commonly used to image it and indicate that using both may yield a more comprehensive visualization of the SN.

Analyzing functional magnetic resonance imaging (fMRI) time courses with dynamic approaches has generated a great deal of interest because of the additional temporal features that can be extracted. In this work, to systemically model spatiotemporal patterns of the brain, a Gaussian hidden Markov model (GHMM) was adopted to model the brain state switching process. We assumed that the brain switches among a number of different brain states as a Markov process and used multivariate Gaussian distributions to represent the spontaneous activity patterns of brain states. This model was applied to resting-state fMRI data from 100 subjects in the Human Connectome Project and detected nine highly reproducible brain states and their temporal and transition characteristics. Our results indicate that the GHMM can unveil brain dynamics that may provide additional insights regarding the brain at resting state.

Objective To analyze diffusion tensor imaging (DTI) data in the substantia nigra (SN) using a more consistent region of interest defined by neuromelanin-sensitive MRI in order to assess Parkinson's disease (PD) related changes in diffusion characteristics in the SN. Methods T1-weighted and DTI data were obtained in a cohort of 37 subjects (20 control subjects and 17 subjects with PD). The subjects in the PD group were clinically diagnosed PD patients with an average Unified Parkinsonian Disease Rating Scale (UPDRS)-III score of 23.2±9.3. DTI data were analyzed using SN ROIs defined by neuromelanin-sensitive MRI and, for comparison, with ROIs defined on T2-weighted images (b=0 images). Results Compared to control subjects, significantly lower fractional anisotropy was observed in PD in the neuromelanin SN ROI but not in the ROI derived from the T2-weighted image. This decrease was largest in the rostral and lateral portions of the neuromelanin volume, which were found to have more hypointensity in the T2-weighted image and, presumably, higher iron content in the PD group. In addition, a larger decrease in fractional anisotropy was seen in the SN region of interest on the side contralateral to the side exhibiting more severe symptoms. These results indicate that the use of neuromelanin sensitive MRI to define the ROI in the SN for analyzing DTI data leads to more significant results, enhancing the robustness of DTI study and DTI based biomarkers of PD.