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Substance use may confound the study of brain structure in schizophrenia. We used voxel-based morphometry (VBM) to examine whether differences in regional gray matter volumes exist between schizophrenia patients with (n = 92) and without (n = 66) clinically significant cannabis and/or alcohol use histories compared to 88 healthy control subjects. Relative to controls, patients with schizophrenia had reduced gray matter volume in the bilateral precentral gyrus, right medial frontal cortex, right visual cortex, right occipital pole, right thalamus, bilateral amygdala, and bilateral cerebellum regardless of substance use history. Within these regions, we found no volume differences between patients with schizophrenia and a history of cannabis and/or alcohol compared to patients with schizophrenia without a clinically significant substance use history. Our data support the idea that a clinically meaningful history of alcohol or cannabis use does not significantly compound the gray matter deficits associated with schizophrenia.
Copyright © 2018. Published by Elsevier B.V.
BACKGROUND - Vascular pathology is common in late-life depression (LLD) and may contribute to alterations in cerebral blood flow (CBF) and cerebrovascular reactivity (CVR). In turn, such hemodynamic deficits may adversely affect brain function and clinical course. The goal of this study was to examine whether altered cerebral hemodynamics in depressed elders predicted antidepressant response.
METHODS - 21 depressed elders completed cranial 3T MRI, including a pseudo-continuous Arterial Spin Labeling (pcASL) acquisition on both room air and during a hypercapnia challenge. Participants then completed 12 weeks of open-label sertraline. Statistical analyses examined the relationship between regional normalized CBF and CVR values and change in Montgomery-Asberg Depression Rating Scale (MADRS) and tested for differences based on remission status.
RESULTS - 10 participants remitted and 11 did not. After controlling for age and baseline MADRS, greater change in MADRS with treatment was associated with lower pre-treatment normalized CBF in the caudal anterior cingulate cortex (cACC) and lateral orbitofrontal cortex (OFC), as well as lower CVR with hypercapnia in the caudal medial frontal gyrus (cMFG). After controlling for age and baseline MADRS score, remitters exhibited lower CBF in the cACC and lower CVR in the cMFG.
LIMITATIONS - Our sample was small, did not include a placebo arm, and we examined only specific regions of interest.
CONCLUSIONS - Our findings suggest that increased perfusion of the OFC and the ACC is associated with a poor antidepressant response. They do not support that vascular pathology as measured by CBF and CVR negatively affects acute treatment outcomes.
Published by Elsevier B.V.
We investigated the chronometry of neural processes in frontal eye fields of macaques performing double-step saccade visual search in which a conspicuous target changes location in the array on a random fraction of trials. Durations of computational processes producing a saccade to original and final target locations (GO1 and GO2, respectively) are derived from response times (RT) on different types of trials. In these data, GO2 tended to be faster than GO1, demonstrating that inhibition of the initial saccade did not delay production of the compensated saccade. Here, we measured the dynamics of visual, visuomovement, and movement neuron activity in relation to these processes by examining trials when neurons instantiated either process. First, we verified that saccades were initiated when the discharge rate of movement neurons reached a threshold that was invariant across RT and trial type. Second, the time when visual and visuomovement neurons selected the target and when movement neuron activity began to accumulate were not significantly different across trial type. Third, the interval from the beginning of accumulation to threshold of movement-related activity was significantly shorter when instantiating the GO2 relative to the GO1 process. Differences observed between monkeys are discussed. Fourth, random variation of RT was accounted for to some extent by random variation in both the onset and duration of selective activity of each neuron type but mostly by variation of movement neuron accumulation duration. These findings offer new insights into the sources of control of target selection and saccade production in dynamic environments.
Copyright © 2016 the American Physiological Society.
The key idea of statistical hypothesis testing is to fix, and thereby control, the Type I error (false positive) rate across samples of any size. Multiple comparisons inflate the global (family-wise) Type I error rate and the traditional solution to maintaining control of the error rate is to increase the local (comparison-wise) Type II error (false negative) rates. However, in the analysis of human brain imaging data, the number of comparisons is so large that this solution breaks down: the local Type II error rate ends up being so large that scientifically meaningful analysis is precluded. Here we propose a novel solution to this problem: allow the Type I error rate to converge to zero along with the Type II error rate. It works because when the Type I error rate per comparison is very small, the accumulation (or global) Type I error rate is also small. This solution is achieved by employing the likelihood paradigm, which uses likelihood ratios to measure the strength of evidence on a voxel-by-voxel basis. In this paper, we provide theoretical and empirical justification for a likelihood approach to the analysis of human brain imaging data. In addition, we present extensive simulations that show the likelihood approach is viable, leading to "cleaner"-looking brain maps and operational superiority (lower average error rate). Finally, we include a case study on cognitive control related activation in the prefrontal cortex of the human brain.
Copyright © 2015 Elsevier Inc. All rights reserved.
Historically, the human frontal pole (FP) has been considered as a single architectonic area. Brodmann's area 10 is located in the frontal lobe with known contributions in the execution of various higher order cognitive processes. However, recent cytoarchitectural studies of the FP in humans have shown that this portion of cortex contains two distinct cytoarchitectonic regions. Since architectonic differences are accompanied by differential connectivity and functions, the frontal pole qualifies as a candidate region for exploratory parcellation into functionally discrete sub-regions. We investigated whether this functional heterogeneity is reflected in distinct segregations within cytoarchitectonically defined FP-areas using meta-analytic co-activation based parcellation (CBP). The CBP method examined the co-activation patterns of all voxels within the FP as reported in functional neuroimaging studies archived in the BrainMap database. Voxels within the FP were subsequently clustered into sub-regions based on the similarity of their respective meta-analytically derived co-activation maps. Performing this CBP analysis on the FP via k-means clustering produced a distinct 3-cluster parcellation for each hemisphere corresponding to previously identified cytoarchitectural differences. Post-hoc functional characterization of clusters via BrainMap metadata revealed that lateral regions of the FP mapped to memory and emotion domains, while the dorso- and ventromedial clusters were associated broadly with emotion and social cognition processes. Furthermore, the dorsomedial regions contain an emphasis on theory of mind and affective related paradigms whereas ventromedial regions couple with reward tasks. Results from this study support previous segregations of the FP and provide meta-analytic contributions to the ongoing discussion of elucidating functional architecture within human FP.
Copyright © 2015 Elsevier Inc. All rights reserved.
Executive control and flexible adjustment of behavior following errors are essential to adaptive functioning. Loss of adaptive control may be a biomarker of a wide range of neuropsychiatric disorders, particularly in the schizophrenia spectrum. Here, we provide support for the view that oscillatory activity in the frontal cortex underlies adaptive adjustments in cognitive processing following errors. Compared with healthy subjects, patients with schizophrenia exhibited low frequency oscillations with abnormal temporal structure and an absence of synchrony over medial-frontal and lateral-prefrontal cortex following errors. To demonstrate that these abnormal oscillations were the origin of the impaired adaptive control in patients with schizophrenia, we applied noninvasive dc electrical stimulation over the medial-frontal cortex. This noninvasive stimulation descrambled the phase of the low-frequency neural oscillations that synchronize activity across cortical regions. Following stimulation, the behavioral index of adaptive control was improved such that patients were indistinguishable from healthy control subjects. These results provide unique causal evidence for theories of executive control and cortical dysconnectivity in schizophrenia.
Neocortex is striking in its laminar architecture. Tracer studies have uncovered anatomical connectivity among laminae, but the functional connectivity between laminar compartments is still largely unknown. Such functional connectivity can be discerned through spontaneous neural correlations during rest. Previous work demonstrated a robust pattern of mesoscopic resting-state connectivity in macaque primary visual cortex (V1) through interlaminar cross-frequency coupling. Here we investigated whether this pattern generalizes to other cortical areas by comparing resting-state laminar connectivity between V1 and the supplementary eye field (SEF), a frontal area lacking a granular layer 4 (L4). Local field potentials (LFPs) were recorded with linear microelectrode arrays from all laminae of granular V1 and agranular SEF while monkeys rested in darkness. We found substantial differences in the relationship between the amplitude of gamma-band (>30 Hz) LFP and the phase of alpha-band (7-14 Hz) LFP between these areas. In V1, gamma amplitudes in L2/3 and L5 were coupled with alpha-band LFP phase in L5, as previously described. In contrast, in SEF phase-amplitude coupling was prominent within L3 and much weaker across layers. These results suggest that laminar interactions in agranular SEF are unlike those in granular V1. Thus the intrinsic functional connectivity of the cortical microcircuit does not seem to generalize across cortical areas.
Copyright © 2015 the American Physiological Society.
OBJECT - The dominant hemisphere frontal operculum may contain critical speech and language pathways, and due to these properties, patients with tumors of the opercular region may be at higher risk for postoperative speech dysfunction. However, the likelihood of incurring temporary or permanent language dysfunction is unknown.
METHODS - The authors retrospectively analyzed their cohort of patients with frontal gliomas to identify those tumors that predominantly involved the dominant frontal operculum. Each tumor was classified as involving the pars orbitalis, pars triangularis, pars opercularis, or a combination of some or all of these areas. The authors then identified and compared characteristics between those patients experiencing transient or permanent speech deficits, as opposed to those with no language dysfunction.
RESULTS - Forty-three patients were identified for inclusion in this analysis. Transient deficits occurred in 12 patients (27.9%), while 4 patients (9.8%) had persistent deficits involving language. Individuals with preoperative language deficits and patients with seizures characterized by speech dysfunction appear to be at the highest risk to develop a deficit (relative risks 3.09 and 1.75, respectively). No patient with a tumor involving the pars orbitalis experienced a persistent deficit.
CONCLUSIONS - Resection of gliomas is widely recognized as a critical element of improved outcome. Given the low rate of language morbidity reported in this group of patients, resection of gliomas within the dominant frontal operculum is well-tolerated with acceptable morbidity and, in this particular location, should not be a deterrent in the overall management of these tumors.
OBJECTIVE - Older adults with major depressive disorder (MDD) experience poor cognitive and behavioral outcomes as MDD occurs in the context of other age-related brain changes. Patients with depression often have impairments on measures of frontal lobe functioning such as working memory. Understanding the effects of depression on cognitive functioning in older adults is important for the development of treatment strategies that focus on cognitive changes as well as mood.
METHODS - Eleven older adults with current MDD and 12 nondepressed comparison participants (all aged 60 years and older) performed the N-back test of working memory during fMRI.
RESULTS - Depressed older adults performed worse than nondepressed participants on the N-back task. Depressed older adults had decreased lateral frontal and parietal activation during the most difficult working memory load condition on the N-back compared with nondepressed older adults.
CONCLUSION - Cognitive dysfunction in geriatric depression may be related to reorganization of brain networks involved in working memory.
Copyright © 2015 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.
We investigated whether a frontal area that lacks granular layer IV, supplementary eye field, exhibits features of laminar circuitry similar to those observed in primary sensory areas. We report, for the first time, visually evoked local field potentials (LFPs) and spiking activity recorded simultaneously across all layers of agranular frontal cortex using linear electrode arrays. We calculated current source density from the LFPs and compared the laminar organization of evolving sinks to those reported in sensory areas. Simultaneous, transient synaptic current sinks appeared first in layers III and V followed by more prolonged current sinks in layers I/II and VI. We also found no variation of single- or multi-unit visual response latency across layers, and putative pyramidal neurons and interneurons displayed similar response latencies. Many units exhibited pronounced discharge suppression that was strongest in superficial relative to deep layers. Maximum discharge suppression also occurred later in superficial than in deep layers. These results are discussed in the context of the canonical cortical microcircuit model originally formulated to describe early sensory cortex. The data indicate that agranular cortex resembles sensory areas in certain respects, but the cortical microcircuit is modified in nontrivial ways.