Dissociable cortico-striatal connectivity abnormalities in major depression in response to monetary gains and penalties.

BACKGROUND: Individuals with major depressive disorder (MDD) are characterized by maladaptive responses to both positive and negative outcomes, which have been linked to localized abnormal activations in cortical and striatal brain regions. However, the exact neural circuitry implicated in such abnormalities remains largely unexplored. METHOD: In this study 26 unmedicated adults with MDD and 29 matched healthy controls (HCs) completed a monetary incentive delay task during functional magnetic resonance imaging (fMRI). Psychophysiological interaction (PPI) analyses probed group differences in connectivity separately in response to positive and negative outcomes (i.e. monetary gains and penalties). RESULTS: Relative to HCs, MDD subjects displayed decreased connectivity between the caudate and dorsal anterior cingulate cortex (dACC) in response to monetary gains, yet increased connectivity between the caudate and a different, more rostral, dACC subregion in response to monetary penalties. Moreover, exploratory analyses of 14 MDD patients who completed a 12-week, double-blind, placebo-controlled clinical trial after the baseline fMRI scans indicated that a more normative pattern of cortico-striatal connectivity pre-treatment was associated with greater improvement in symptoms 12 weeks later. CONCLUSIONS: These results identify the caudate as a region with dissociable incentive-dependent dACC connectivity abnormalities in MDD, and provide initial evidence that cortico-striatal circuitry may play a role in MDD treatment response. Given the role of cortico-striatal circuitry in encoding action-outcome contingencies, such dysregulated connectivity may relate to the prominent disruptions in goal-directed behavior that characterize MDD.

Age-related adaptations of brain function during a memory task are also present at rest.

Several studies have demonstrated age-related regional differences in the magnitude of the BOLD signal using task-based fMRI. It has been suggested that functional changes reflect either compensatory or de-differentiation mechanisms, both of which assume response to a specific stimulus. Here, we have tested whether ageing affects both task-based and resting brain function, and the extent to which functional changes are mediated by reductions in grey matter (GM) volume. Two groups, of 22 healthy younger and 22 older volunteers, underwent an imaging protocol involving structural and functional MRI, both during a memory task and at rest. The two groups had similar socio-demographical characteristics and cognitive performance. Image analysis revealed both structural and functional differences. Increased BOLD signal in older relative to younger volunteers was mainly observed in the frontal lobes, both during the task and at rest. Functional changes in the frontal lobes were largely located in brain regions spared from GM loss, and adding GM covariates to the fMRI analysis did not significantly alter the group differences. Our results are consistent with the suggestion that, during normal ageing, the brain responds to neuronal loss by fine-tuning connections between spared neurons. Longitudinal studies will be necessary to fully test this hypothesis.

Functional disconnection between the visual cortex and right fusiform face area in schizophrenia.

Patients with schizophrenia show impairment in processing faces, including facial affect and face detection, but the underlying mechanisms are unknown. We used functional magnetic resonance imaging (fMRI) to characterize resting state functional connectivity between an independent component analysis (ICA)-defined early visual cortical network (corresponding to regions in V1, V2, V3) and a priori defined face-processing regions (fusiform face area [FFA], occipital face area [OFA], superior temporal sulcus [STS] and amygdala) using dual regression in 20 schizophrenia patients and 26 healthy controls. We also investigated the association between resting functional connectivity and neural responses (fMRI) elicited by a face detection paradigm in a partially overlapping sample (Maher et al., 2016) that used stimuli equated for lower-level perceptual abilities. Group differences in functional connectivity were found in right FFA only; controls showed significantly stronger functional connectivity to an early visual cortical network. Functional connectivity in right FFA was associated with (a) neural responses during face detection in controls only, and (b) perceptual detection thresholds for faces in patients only. The finding of impaired functional connectivity for right FFA (but not other queried domain-specific regions) converges with findings investigating face detection in an overlapping sample in which dysfunction was found exclusively for right FFA in schizophrenia during face detection.

Greater sensitivity of the cortical face processing system to perceptually-equated face detection.

Face detection, the perceptual capacity to identify a visual stimulus as a face before probing deeper into specific attributes (such as its identity or emotion), is essential for social functioning. Despite the importance of this functional capacity, face detection and its underlying brain mechanisms are not well understood. This study evaluated the roles that the cortical face processing system, which is identified largely through studying other aspects of face perception, play in face detection. Specifically, we used functional magnetic resonance imaging (fMRI) to examine the activations of the fusifom face area (FFA), occipital face area (OFA) and superior temporal sulcus (STS) when face detection was isolated from other aspects of face perception and when face detection was perceptually-equated across individual human participants (n=20). During face detection, FFA and OFA were significantly activated, even for stimuli presented at perceptual-threshold levels, whereas STS was not. During tree detection, however, FFA and OFA were responsive only for highly salient (i.e., high contrast) stimuli. Moreover, activation of FFA during face detection predicted a significant portion of the perceptual performance levels that were determined psychophysically for each participant. This pattern of result indicates that FFA and OFA have a greater sensitivity to face detection signals and selectively support the initial process of face vs. non-face object perception.

Cortical thinness and volume differences associated with marijuana abuse in emerging adults.

BACKGROUND: The prevalence of marijuana (MJ) use among youth and its legalization for medical or recreational use has intensified public health endeavors of understanding MJ effects on brain structure and function. Studies indicate that MJ use is related to impaired cognitive performance, and altered functional brain activation and chemistry in adolescents and adults, but MJ effects on brain morphology in emerging adults are less understood. METHODS: Fifteen MJ users (age 21.8±3.6, 2 females) and 15 non-user (NU) participants (age 22.3±3.5, 2 females) were included, demographically matched on age, education and alcohol use. High-resolution structural MR images were acquired at 3Tesla. Cortical thickness (CT) and volumetric analyses were performed using Freesurfer. A priori regions of interest (ROI) included orbitofrontal and cingulate cortices, amygdala, hippocampus and thalamus. RESULTS: Whole brain CT analysis did not result in significant group differences in a priori ROIs but revealed MJ users had significantly less CT (i.e., thinness) in right fusiform gyrus (rFG) compared to NU (p<0.05). Thalamic volume was significantly smaller in MJ users compared to NU (right, p=0.05; left, p=0.01) and associated with greater non-planning (p<0.01) and overall impulsivity (p=0.04). There were no other group differences. CONCLUSIONS: RFG cortical thinness and smaller thalamic volume in emerging adults is associated with MJ abuse. Furthermore, smaller thalamic volume associated with greater impulsivity contributes to growing evidence that the thalamus is neurobiologically perturbed by MJ use. Collectively, altered thalamic and rFG structural integrity may interfere with their known roles in regulating visuoperceptual and object information processing.

Basic principles and neurosurgical applications of positron emission tomography.

Positron emission tomography (PET) is a technique for studying functional processes in the human body in vivo. The important clinical applications of PET in neurosurgery include localization of epileptic foci, diagnosis of brain tumors, preoperative brain mapping, and the study of plasticity of the brain following brain damage. The basic physics and neurosurgical applications of PET are presented.

Differential effects of acute stress on anticipatory and consummatory phases of reward processing.

Anhedonia is one of the core symptoms of depression and has been linked to blunted responses to rewarding stimuli in striatal regions. Stress, a key vulnerability factor for depression, has been shown to induce anhedonic behavior, including reduced reward responsiveness in both animals and humans, but the brain processes associated with these effects remain largely unknown in humans. Emerging evidence suggests that stress has dissociable effects on distinct components of reward processing, as it has been found to potentiate motivation/'wanting' during the anticipatory phase but reduce reward responsiveness/'liking' during the consummatory phase. To examine the impact of stress on reward processing, we used a monetary incentive delay (MID) task and an acute stress manipulation (negative performance feedback) in conjunction with functional magnetic resonance imaging (fMRI). Fifteen healthy participants performed the MID task under no-stress and stress conditions. We hypothesized that stress would have dissociable effects on the anticipatory and consummatory phases in reward-related brain regions. Specifically, we expected reduced striatal responsiveness during reward consumption (mirroring patterns previously observed in clinical depression) and increased striatal activation during reward anticipation consistent with non-human findings. Supporting our hypotheses, significant Phase (Anticipation/Consumption)×Stress (Stress/No-stress) interactions emerged in the putamen, nucleus accumbens, caudate and amygdala. Post hoc tests revealed that stress increased striatal and amygdalar activation during anticipation but decreased striatal activation during consumption. Importantly, stress-induced striatal blunting was similar to the profile observed in clinical depression under baseline (no-stress) conditions in prior studies. Given that stress is a pivotal vulnerability factor for depression, these results offer insight to better understand the etiology of this prevalent disorder.

Effect of partition coefficient, permeability surface product, and radioisotope on the signal-to-noise ratio in PET functional brain mapping: a computer simulation.

In this work we use a computer simulation to estimate the magnitude of improvement in the signal-to-noise ratio of PET functional brain mapping studies as a function of partition coefficient and permeability surface product for O-14, F-17, and O-15 labeled flow tracers. A model for signal-to-noise ratio is derived from the Kety model for inert diffusible blood flow tracers. The results of the simulation suggest that moderate increases in partition coefficient and permeability surface product compared with water would lead to an increase in signal-to-noise ratio of a factor of about 3.

The pharmacokinetics of hyperpolarized xenon: implications for cerebral MRI.

In this work, a compartmental model to predict the concentration of hyperpolarized xenon (Xe) in the brain is developed based on the well established kinetics of Xe and estimated T1 values for the compartments. For the gaseous compartments, T1 was set to 12 seconds. For the tissue compartments, T1 was set to 6 seconds. Three gas delivery techniques were modeled: hyperventilation followed by breath-hold, continual breathing, and hyperventilation followed by continual breathing. Based on Xe CT, it is estimated that the maximum concentration of Xe that could be breathed is 80%. Based on this value and the estimated maximum polarization of 50%, the peak gray matter concentration of hyperpolarized Xe is calculated to be .036 mM. This leads to an estimated signal-to-noise ratio (SNR), at 2 T, for hyperpolarized Xe that is a factor of 50 lower than the SNR for proton MRI. The peak concentration of hyperpolarized Xe was also calculated over a wide range of gas and tissue T1 values. This model also predicts that the arterial blood will have a concentration of hyperpolarized Xe that is 10 times greater than the concentration in gray matter. An interactive version of the model can be found on the World Wide Web at http:(/)/ric.uthscsa.edu/staff /charlesmartinphd.html.

Comparison of the temporal response in perfusion and BOLD-based event-related functional MRI.

Event-related functional MRI (ER-fMRI) based on both blood oxygen level-dependent (BOLD) contrast and perfusion contrast has been recently developed to study human brain activation due to brief stimulation. In this report, both BOLD- and perfusion-based ER-fMRI were directly compared using repeated single-trial, short visual stimulation (1 sec) in six human volunteers. The results show that the cerebral blood flow change reached a maximum approximately 1 sec earlier than the BOLD signal change (4.2 +/- 0.2 sec vs. 5.1 +/- 0.2 sec after the stimulation, P < 0.05). The full width at half maximum of the hemodynamic response measured by perfusion was not significantly different from that measured with BOLD (5.1 +/- 0.6 sec vs. 5.9 +/- 0.6 sec). A positive linear correlation was found between the maximum perfusion and maximum BOLD signal changes (r = 0. 77, P = 0.07).

A tool for comparison of PET and fMRI methods: calculation of the uncertainty in the location of an activation site in a PET image.

A technique for calculating the uncertainty in the location of an activation site in a PET image, without performing repeated measures, is presented. With the development of new fMRI methods for measuring cerebral hemodynamics, demonstration of the efficacy of these techniques will be critical to establish clinical utility. Comparisons with PET are a powerful tool for validating these new fMRI techniques. In addition to the fact that PET techniques are well-established methods for making physiological measurements in vivo, PET methods are also free of the geometric distortions and nonuniform signal-to-noise artifacts (due to signal dropout) common in fMRI techniques. Comparisons reported previously have been limited by the large number of trials acquired in single-subject fMRI studies and the small number of trials in a PET study (due to the radiation dose to the patient or the interscan delays for tracer decay). Our method calculates both the center of mass (CM) of a predefined region of interest and the uncertainty in the location of the CM using the preimage PET data (sinograms). Results of phantom studies demonstrate that our method is an unbiased measurement equivalent to that of repeated measures with a large number of images. Extension of this technique to estimate the uncertainty in the location of an activation site in a PET statistical parametric map will permit precise rigorous comparisons of PET and fMRI methods in single subjects without the constraints imposed by the relatively small number of PET measurements.