Studies of conceptual processing have revealed that the prefrontal cortex is implicated in close-ended, deliberate memory retrieval, especially the left ventrolateral prefrontal regions. However, much of human thought—particularly that which is characterized as creative—requires more open-ended, spontaneous memory retrieval. To explore the neural systems that support conceptual processing under these two distinct circumstances, we obtained functional magnetic resonance images from 24 participants either while retrieving the common use of an everyday object (e.g., “blowing your nose,” in response to a picture of a tissue) or while generating a creative (i.e., uncommon but plausible) use for it (e.g., “protective padding in a package”). The patterns of activation during open- and closed-ended tasks were reliably different, with regard to the magnitude of anterior versus posterior activation. Specifically, the close-ended task (i.e., Common Use task) reliably activated regions of lateral prefrontal cortex, whereas the open-ended task (i.e., Uncommon Use task) reliably activated regions of occipito-temporal cortex. Furthermore, there was variability across subjects in the types of responses produced on the open-ended task that was associated with the magnitude of activation in the middle occipital gyrus on this task. The present experiment is the first to demonstrate a dynamic tradeoff between anterior frontal and posterior occipitotemporal regions brought about by the close- or open-ended task demands.
cognitive flexibility; lateral occipital-temporal cortex; inferior frontal gyrus; creative object use; semantic knowledge
This study investigated the preparatory control of motor inhibition and motor execution using a stop signal task (SST) and functional magnetic resonance imaging (fMRI). In the SST, a frequent “go” signal triggered a prepotent response and a less frequent “stop” signal prompted the inhibition of this response. Preparatory control of motor inhibition and execution in the stop signal trials were examined by contrasting brain activation between stop success and stop error trials during the fore-period, in which participants prepared to respond to go or to stop. Results from 91 healthy adults showed greater activation in the right prefrontal cortex and inferior parietal lobule during preparatory motor inhibition. Preparatory motor execution activated bilateral putamen, primary motor cortices, posterior cingulate cortex, ventromedial prefrontal cortex, and superior temporal/intraparietal sulci. Furthermore, the extents of these inhibition and execution activities were inversely correlated across subjects. On the basis of a median split of the stop signal reaction time (SSRT), subjects with short SSRT showed greater activity in the right orbital frontal cortex during preparatory inhibition. These new findings suggest that the go and stop processes interact prior to target presentation in the SST, in accord with recent computational models of stop signal inhibition.
stop signal; inhibitory control; proactive; prefrontal; race model; go/no-go
Rare autosomal dominant mutations result in familial Alzheimer’s disease (FAD) with a relatively consistent age of onset within families. This provides an estimate of years until disease onset (relative age) in mutation carriers. Increased AD risk has been associated with differences in functional magnetic resonance imaging (fMRI) activity during memory tasks, but most of these studies have focused on possession of apolipoprotein E allele 4 (APOE4), a risk factor, but not causative variant, of late-onset AD. Evaluation of fMRI activity in presymptomatic FAD mutation carriers versus noncarriers provides insight into preclinical changes in those who will certainly develop AD in a prescribed period of time. Adults from FAD mutation-carrying families (nine mutation carriers, eight noncarriers) underwent fMRI scanning while performing a memory task. We examined fMRI signal differences between carriers and noncarriers, and how signal related to fMRI task performance within mutation status group, controlling for relative age and education. Mutation noncarriers had greater retrieval period activity than carriers in several AD-relevant regions, including the left hippocampus. Better performing noncarriers showed greater encoding period activity including in the parahippocampal gyrus. Poorer performing carriers showed greater retrieval period signal, including in the frontal and temporal lobes, suggesting underlying pathological processes.
early onset; functional magnetic resonance imaging; PSEN1; APP; mutation; hippocampus; medial temporal lobe; volume
Very little is known on white collar crime and how it differs to other forms of offending. This study tests the hypothesis that white collar criminals have better executive functioning, enhanced information processing, and structural brain superiorities compared to offender controls. Using a case-control design, executive functioning, orienting, and cortical thickness was assessed in 21 white collar criminals matched with 21 controls on age, gender, ethnicity, and general level of criminal offending. White collar criminals had significantly better executive functioning, increased electrodermal orienting, increased arousal, and increased cortical gray matter thickness in the ventromedial prefrontal cortex, inferior frontal gyrus, somatosensory cortex, and the temporal-parietal junction compared to controls. Results, while initial, constitute the first findings on neurobiological characteristics of white-collar criminals It is hypothesized that white collar criminals have information-processing and brain superiorities that give them an advantage in perpetrating criminal offenses in occupational settings.
antisocial; ventromedial; inferior frontal; temporal-parietal; somatosensory; orienting; arousal; electrodermal
Fluid intelligence represents the capacity for flexible problem solving and rapid behavioral adaptation. Rewards drive flexible behavioral adaptation, in part via a teaching signal expressed as reward prediction errors in the ventral striatum, which has been associated with phasic dopamine release in animal studies. We examined a sample of 28 healthy male adults using multimodal imaging and biological parametric mapping with 1) functional magnetic resonance imaging during a reversal learning task and 2) in a subsample of 17 subjects also with positron emission tomography using 6-[18F]fluoro-L-DOPA to assess dopamine synthesis capacity. Fluid intelligence was measured using a battery of nine standard neuropsychological tests. Ventral striatal BOLD correlates of reward prediction errors were positively correlated with fluid intelligence and, in the right ventral striatum, also inversely correlated with dopamine synthesis capacity (FDOPA Kinapp). When exploring aspects of fluid intelligence, we observed that prediction error signaling correlates with complex attention and reasoning. These findings indicate that individual differences in the capacity for flexible problem solving may be driven by ventral striatal activation during reward-related learning, which in turn proved to be inversely associated with ventral striatal dopamine synthesis capacity.
prediction error; dopamine synthesis; fluid intelligence; ventral striatum; fMRI; PET
Connectivity analyses and computational modeling of human brain function from fMRI data frequently require the specification of regions of interests (ROIs). Several analyses have relied on atlases derived from anatomical or cyto-architectonic boundaries to specify these ROIs, yet the suitability of atlases for resting state functional connectivity studies has yet to be established. This paper introduces a data-driven method for generating an ROI atlas by parcellating whole brain resting-state fMRI data into spatially coherent regions of homogeneous functional connectivity. Several clustering statistics are used to compare methodological trade-offs as well as determine an adequate number of clusters. Additionally, we evaluate the suitability of the parcellation atlas against four ROI atlases (Talairach and Tournoux, Harvard-Oxford, Eickoff-Zilles, and Automatic Anatomical Labeling) and a random parcellation approach. The evaluated anatomical atlases exhibit poor ROI homogeneity and do not accurately reproduce functional connectivity patterns present at the voxel scale. In general, the proposed functional and random parcellations perform equivalently for most of the metrics evaluated. ROI size and hence the number of ROIs in a parcellation had the greatest impact on their suitability for functional connectivity analysis. With 200 or fewer ROIs, the resulting parcellations consist of ROIs with anatomic homology, and thus offer increased interpretability. Parcellation results containing higher numbers of ROIs (600 or 1000) most accurately represent functional connectivity patterns present at the voxel scale and are preferable when interpretability can be sacrificed for accuracy. The resulting atlases and clustering software have been made publicly available at: http://www.nitrc.org/projects/cluster_roi/.
resting state; functional connectivity; regions of interest; clustering; atlas
Cortical thickness mapping is a widely used method for the analysis of neuroanatomical differences between subject groups. We applied power analysis methods over a range of image processing parameters to derive a model that allows researchers to calculate the number of subjects required to ensure a well-powered cross-sectional cortical thickness study.
0.9-mm isotropic T1-weighted 3D MPRAGE MRI scans from 98 controls (53 females, age 29.1 ± 9.7 years) were processed using Freesurfer 5.0. Power analyses were carried out using vertex-wise variance estimates from the coregistered cortical thickness maps, systematically varying processing parameters. A genetic programming approach was used to derive a model describing the relationship between sample size and processing parameters. The model was validated on four Alzheimer’s Disease Neuroimaging Initiative control datasets (mean 126.5 subjects/site, age 76.6 ± 5.0 years).
Approximately 50 subjects per group are required to detect a 0.25-mm thickness difference; less than 10 subjects per group are required for differences of 1 mm (two-sided test, 10 mm smoothing, α = 0.05). Sample size estimates were heterogeneous over the cortical surface. The model yielded sample size predictions within 2–6% of that determined experimentally using independent data from four other datasets. Fitting parameters of the model to data from each site reduced the estimation error to less than 2%.
The derived model provides a simple tool for researchers to calculate how many subjects should be included in a well-powered cortical thickness analysis.
MRI; neuroimaging; study design; power analysis; morphometry; cortical thickness
Mild traumatic brain injury (TBI) is a common source of morbidity from the wars in Iraq and Afghanistan. With no overt lesions on structural MRI, diagnosis of chronic mild TBI in military veterans relies on obtaining an accurate history and assessment of behavioral symptoms that are also associated with frequent comorbid disorders, particularly posttraumatic stress disorder (PTSD) and depression. Military veterans from Iraq and Afghanistan with mild TBI (n=30) with comorbid PTSD and depression and non-TBI participants from primary (n=42) and confirmatory (n=28) control groups were assessed with high angular resolution diffusion imaging (HARDI). White matter-specific registration followed by whole-brain voxelwise analysis of crossing fibers provided separate partial volume fractions reflecting the integrity of primary fibers and secondary (crossing) fibers. Loss of white matter integrity in primary fibers (p < .05; corrected) was associated with chronic mild TBI in a widely distributed pattern of major fiber bundles and smaller peripheral tracts including the corpus callosum (genu, body, splenium), forceps minor, forceps major, superior and posterior corona radiata, internal capsule, superior longitudinal fasciculus, and others. Distributed loss of white matter integrity correlated with duration of loss of consciousness and most notably with “feeling dazed or confused,” but not diagnosis of PTSD or depressive symptoms. This widespread spatial extent of white matter damage has typically been reported in moderate to severe TBI. The diffuse loss of white matter integrity appears consistent with systemic mechanisms of damage shared by blast- and impact-related mild TBI that involves a cascade of inflammatory and neurochemical events.
mild traumatic brain injury; high angular resolution diffusion imaging; white matter; crossing fibers; posttraumatic stress disorder
Individuals with heavy prenatal alcohol exposure can experience significant deficits in cognitive and psychosocial functioning and alterations in brain structure that persist into adulthood. In this report, data from 99 participants collected across three sites (Los Angeles and San Diego, California, and Cape Town, South Africa) were analyzed to examine relationships between brain structure, neurocognitive function, facial morphology, and maternal reports of quantities of alcohol consumption during the first trimester. Across study sites, we found highly significant volume reductions in the FASD group for all of the brain regions evaluated. After correcting for scan location, age, and total brain volume, these differences remained significant in some regions of the basal ganglia and diencephalon. In alcohol-exposed subjects, we found that smaller palpebral fissures were significantly associated with reduced volumes in the diencephalon bilaterally, that greater dysmorphology of the philtrum predicted smaller volumes in basal ganglia and diencephalic structures, and that lower IQ scores were associated with both smaller basal ganglia volumes and greater facial dysmorphology. In subjects from South Africa, we found a significant negative correlation between intracranial volume and total number of drinks per week in the first trimester. These results corroborate previous reports that prenatal alcohol exposure is particularly toxic to basal ganglia and diencephalic structures. We extend previous findings by illustrating relationships between specific measures of facial dysmorphology and the volumes of particular subcortical structures, and for the first time show that continuous measures of maternal alcohol consumption during the first trimester relates to overall brain volume reduction.
Prenatal Alcohol Exposure; Teratogenic Effects of alcohol; Facial Abnormalities; Brain Development; Developmental Defects
Sleep spindles are bursts of rhythmic 10–15 Hz activity, lasting ~0.5–2 s, that occur during Stage 2 sleep. They are coherent across multiple cortical and thalamic locations in animals, and across scalp EEG sites in humans, suggesting simultaneous generation across the cortical mantle. However, reports of MEG spindles occurring without EEG spindles, and vice versa, are inconsistent with synchronous distributed generation. We objectively determined the frequency of MEG-only, EEG-only, and combined MEG-EEG spindles in high density recordings of natural sleep in humans. About 50% of MEG spindles occur without EEG spindles, but the converse is rare (~15%). Compared to spindles that occur in MEG only, those that occur in both MEG and EEG have ~1% more MEG coherence and ~15% more MEG power, insufficient to account for the ~55% increase in EEG power. However, these combined spindles involve ~66% more MEG channels, especially over frontocentral cortex. Furthermore, when both MEG and EEG are involved in a given spindle, the MEG spindle begins ~150 ms before the EEG spindle and ends ~250 ms after. Our findings suggest that spindles begin in focal cortical locations which are better recorded with MEG gradiometers than referential EEG due to the biophysics of their propagation. For some spindles, only these regions remain active. For other spindles, these locations may recruit other areas over the next 200 ms, until a critical mass is achieved, including especially frontal cortex, resulting in activation of a diffuse and/or multifocal generator that is best recorded by referential EEG derivations due to their larger leadfields.
synchrony; cortex; thalamus; inverse solution; oscillation; human; sleep; matrix; core; thalamic reticular nucleus; alpha
EEG-fMRI in epileptic patients is commonly analyzed using the general linear model (GLM), which assumes a known hemodynamic response function (HRF) to epileptic spikes in the EEG. In contrast, independent component analysis (ICA) can extract Blood-Oxygenation Level Dependent (BOLD) responses without imposing constraints on the HRF. This technique was evaluated on data generated by superimposing artificial responses on real background fMRI signals. Simulations were run using a wide range of EEG spiking rates, HRF amplitudes, and activation regions. The data were decomposed by spatial ICA into independent components. A deconvolution method then identified component time courses significantly related to the simulated spikes, without constraining the shape of the HRF. Components matching the simulated activation regions (“concordant components”) were found in 84.4% of simulations, while components at discordant locations were found in 12.2% of simulations. These false activations were often related to large artifacts that coincidentally occurred simultaneously with some of the random simulated spikes. The performance of the method depended closely on the simulation parameters; when the number of spikes was low, concordant components could only be identified when HRF amplitudes were large. Although ICA did not depend on the shape of the HRF, data processed with the GLM did not reveal the appropriate activation region when the HRF varied slightly from the canonical shape used in the model. ICA may thus be able to extract BOLD responses from EEG-fMRI data in epileptic patients, in a way that is robust to uncertainty and variability in the shape of the HRF.
PMID: 18726909 CAMSID: cams3467
independent component analysis; EEG-fMRI; epilepsy; deconvolution; hemodynamic response function
Current theories suggest that disrupting cortical information integration may account for the mechanism of general anesthesia in suppressing consciousness. Human cognitive operations take place in hierarchically structured neural organizations in the brain. The process of low-order neural representation of sensory stimuli becoming integrated in high-order cortices is also known as cognitive binding. Combining neuroimaging, cognitive neuroscience, and anesthetic manipulation, we examined how cognitive networks involved in auditory verbal memory are maintained in wakefulness, disrupted in propofol-induced deep sedation, and re-established in recovery. Inspired by the notion of cognitive binding, an fMRI-guided connectivity analysis was utilized to assess the integrity of functional interactions within and between different levels of the task-defined brain regions. Task-related responses persisted in the primary auditory cortex (PAC), but vanished in the inferior frontal gyrus (IFG) and premotor areas in deep sedation. For connectivity analysis, seed regions representing sensory and high-order processing of the memory task were identified in the PAC and IFG. Propofol disrupted connections from the PAC seed to the frontal regions and thalamus, but not the connections from the IFG seed to a set of widely distributed brain regions in the temporal, frontal, and parietal lobes (with exception of the PAC). These later regions have been implicated in mediating verbal comprehension and memory. These results suggest that propofol disrupts cognition by blocking the projection of sensory information to high-order processing networks and thus preventing information integration. Such findings contribute to our understanding of anesthetic mechanisms as related to information and integration in the brain.
propofol sedation; verbal memory; information and integration; cognitive binding; fMRI-guided connectivity analysis
Autonomic nervous system (ANS) response to acupuncture has been investigated by multiple studies; however, the brain circuitry underlying this response is not well understood. We applied event-related fMRI (er-fMRI) in conjunction with ANS recording (heart rate, HR; skin conductance response, SCR). Brief manual acupuncture stimuli were delivered at acupoints ST36 and SP9, while sham stimuli were delivered at control location, SH1. Acupuncture produced activation in S2, insula, and mid-cingulate cortex, and deactivation in default mode network (DMN) areas. On average, HR deceleration (HR–) and SCR were noted following both real and sham acupuncture, though magnitude of response was greater following real acupuncture and inter-subject magnitude of response correlated with evoked sensation intensity. Acupuncture events with strong SCR also produced greater anterior insula activation than without SCR. Moreover, acupuncture at SP9, which produced greater SCR, also produced stronger sharp pain sensation, and greater anterior insula activation. Conversely, acupuncture-induced HR– was associated with greater DMN deactivation. Between-event correlation demonstrated that this association was strongest for ST36, which also produced more robust HR–. In fact, DMN deactivation was significantly more pronounced across acupuncture stimuli producing HR–, versus those events characterized by acceleration (HR+). Thus, differential brain response underlying acupuncture stimuli may be related to differential autonomic outflows and may result from heterogeneity in evoked sensations. Our er-fMRI approach suggests that ANS response to acupuncture, consistent with previously characterized orienting and startle/defense responses, arises from activity within distinct subregions of the more general brain circuitry responding to acupuncture stimuli.
orienting response; defense response; acupoint; skin conductance response; heart rate
Large-scale longitudinal studies of regional brain volume require reliable quantification using automated segmentation and labeling. However, repeated MR scanning of the same subject, even if using the same scanner and acquisition parameters, does not result in identical images due to small changes in image orientation, changes in prescan parameters, and magnetic field instability. These differences may lead to appreciable changes in estimates of volume for different structures. This study examined scan–rescan reliability of automated segmentation algorithms for measuring several subcortical regions, using both within-day and across-day comparison sessions in a group of 23 normal participants. We found that the reliability of volume measures including percent volume difference, percent volume overlap (Dice’s coefficient), and intraclass correlation coefficient (ICC), varied substantially across brain regions. Low reliability was observed in some structures such as the amygdala (ICC = 0.6), with higher reliability (ICC = 0.9) for other structures such as the thalamus and caudate. Patterns of reliability across regions were similar for automated segmentation with FSL/FIRST and FreeSurfer (longitudinal stream). Reliability was associated with the volume of the structure, the ratio of volume to surface area for the structure, the magnitude of the interscan interval, and the method of segmentation. Sample size estimates for detecting changes in brain volume for a range of likely effect sizes also differed by region. Thus, longitudinal research requires a careful analysis of sample size and choice of segmentation method combined with a consideration of the brain structure(s) of interest and the magnitude of the anticipated effects.
structural MRI; FreeSurfer; FSL/FIRST; reliability; scan–rescan; automated segmentation
Structural changes in neuroanatomical subregions can be measured using serial magnetic resonance imaging scans, and provide powerful biomarkers for detecting and monitoring Alzheimer's disease. The Alzheimer's Disease Neuroimaging Initiative (ADNI) has made a large database of longitudinal scans available, with one of its primary goals being to explore the utility of structural change measures for assessing treatment effects in clinical trials of putative disease-modifying therapies. Several ADNI-funded research laboratories have calculated such measures from the ADNI database and made their results publicly available. Here, using sample size estimates, we present a comparative analysis of the overall results that come from the application of each laboratory's extensive processing stream to the ADNI database. Obtaining accurate measures of change requires correcting for potential bias due to the measurement methods themselves; and obtaining realistic sample size estimates for treatment response, based on longitudinal imaging measures from natural history studies such as ADNI, requires calibrating measured change in patient cohorts with respect to longitudinal anatomical changes inherent to normal aging. We present results showing that significant longitudinal change is present in healthy control subjects who test negative for amyloid-β pathology. Therefore, sample size estimates as commonly reported from power calculations based on total structural change in patients, rather than change in patients relative to change in healthy controls, are likely to be unrealistically low for treatments targeting amyloid-related pathology. Of all the measures publicly available in ADNI, thinning of the entorhinal cortex quantified with the Quarc methodology provides the most powerful change biomarker.
MCI; bias; biomarker; clinical trial; disease-specific effect; amyloid; aging; Alzheimer's disease; entorhinal cortex; hippocampus
Epileptic seizures are due to abnormal synchronized neuronal discharges. Techniques measuring electrical changes are commonly used to analyze seizures. Neuronal activity can be also defined by concomitant hemodynamic and metabolic changes. Simultaneous electroencephalogram (EEG)-functional MRI (fMRI) measures noninvasively with a high-spatial resolution BOLD changes during seizures in the whole brain. Until now, only a static image representing the whole seizure was provided. We report in 10 focal epilepsy patients a new approach to dynamic imaging of seizures including the BOLD time course of seizures and the identification of brain structures involved in seizure onset and discharge propagation. The first activation was observed in agreement with the expected location of the focus based on clinical and EEG data (three intracranial recordings), thus providing validity to this approach. The BOLD signal preceded ictal EEG changes in two cases. EEG-fMRI may detect changes in smaller and deeper structures than scalp EEG, which can only record activity form superficial cortical areas. This method allowed us to demonstrate that seizure onset zone was limited to one structure, thus supporting the concept of epileptic focus, but that a complex neuronal network was involved during propagation. Deactivations were also found during seizures, usually appearing after the first activation in areas close or distant to the activated regions. Deactivations may correspond to actively inhibited regions or to functional disconnection from normally active regions. This new noninvasive approach should open the study of seizure generation and propagation mechanisms in the whole brain to groups of patients with focal epilepsies.
PMID: 19507156 CAMSID: cams3405
seizure; epilepsy; imaging; fMRI; EEG
Recent studies have linked alcoholism with a dysfunctional neural reward system. Although several electrophysiological studies have explored reward processing in healthy individuals, such studies in alcohol dependent individuals are quite rare. The present study examines theta oscillations during reward processing in abstinent alcoholics. The electroencephalogram (EEG) was recorded in 38 abstinent alcoholics and 38 healthy controls as they performed a single outcome gambling task which involved outcomes of either loss or gain of an amount (10¢ or 50¢) that was bet. Event-related theta band (3.0–7.0 Hz) power following each outcome stimulus was computed using the S-transform method. Theta power at the time window of the outcome-related negativity (ORN) and positivity (ORP) (200–500 ms) was compared across groups and outcome conditions. Additionally, behavioral data of impulsivity and task performance were analyzed. The alcoholic group showed significantly decreased theta power during reward processing compared to controls. Current Source Density (CSD) maps of alcoholics revealed weaker and diffuse source activity for all conditions and weaker bilateral prefrontal sources during the Loss 50 condition as compared to controls who manifested stronger and focused midline sources. Further, alcoholics exhibited increased impulsivity and risk-taking on the behavioral measures. A strong association between reduced anterior theta power and impulsive task-performance was observed. It is suggested that decreased power and weaker and diffuse CSD in alcoholics may be due to dysfunctional neural reward circuitry. The relationship among alcoholism, theta oscillations, reward processing and impulsivity could offer clues to understand brain circuitries that mediate reward processing and inhibitory control.
Alcoholism; Event-related oscillations (EROs); Theta power; Outcome-related negativity (ORN); Outcome-related positivity (ORP); N2, P3, Error-related negativity (ERN); Medial Frontal Negativity (MFN); Gambling task; Impulsivity; Risk-taking
The gamma band response is thought to be a key neural signature of information processing in the mammalian brain, yet little is known about how age-related maturation influences the gamma-band response. Recent MRI based studies have shown that brain maturation is accompanied by clear structural changes in both grey and white matter, yet the correspondence of these changes to brain function is unclear. The objective of this study was to relate visual cortex (V1) gamma-band responses to age-related structural change.
We evaluated MEG measured gamma-band responses to contrast gratings stimuli and structural MRIs from participants observed from 2 separate research centers (MEG lab at CUBRIC, Cardiff University, UK, and the Lurie Family Foundations MEG Imaging Center, (CHOP) at the Children’s Hospital of Philadelphia). Pooled participant data (N=59) ranged in age from 8.7 to 45.3 yrs.
We assessed linear associations between age and MEG gamma-band frequency and amplitude, as well as between age and MRI volumetric parameters of the occipital lobe. Our MEG findings revealed a significant negative correlation for gamma band frequency vs. age. Volumetric brain analysis from the occipital lobe also revealed significant negative correlations between age and the cortical thickness of pericalcarine and cuneus areas.
Our functional MEG and structural MRI findings shows regionally specific changes due to maturation and may thus be informative for understanding physiological processes of neural development, maturation, and age-related decline. In addition, this study represents (to our knowledge), the first published demonstration of multi-centre data sharing across MEG centers.
Recurrent anticipation of ominous events is central to obsessions, the core symptom of obsessive–compulsive disorder (OCD), yet the neural basis of intrinsic anticipatory processing in OCD is unknown. We studied non-medicated adults with OCD and case matched healthy controls in a visual-spatial working memory task with distractor. Magnetoencephalography was used to examine the medial cortex activity during anticipation of to-be-inhibited distractors and to-be-facilitated retrieval stimuli. In OCD anticipatory activation to distractors was abnormally reduced within the posterior cingulate and fusiform gyrus compared to prominent activation in controls. Conversely, OCD subjects displayed significantly increased activation to retrieval stimuli within the anterior cingulate and supplementary motor cortex. This previously unreported discordant pattern of medial anticipatory activation in OCD was accompanied by normal performance accuracy. While increased anterior cortex activation in OCD is commonly viewed as failure of inhibition, the current pattern of data implicates the operation of an anterior compensatory mechanism amending the posterior medial self-regulatory networks disrupted in OCD.
OCD; MEG; anticipatory top-down control; posterior medial self-regulatory networks; compensatory mechanism
Structural brain deficits, especially fronto-temporal volume reduction and ventricular enlargement, have been repeatedly reported in patients with schizophrenia. However, it remains unclear whether brain structural deformations may be attributable to disease-related or genetic factors. In this study, the structural magnetic resonance imaging data of 48 adult-onset schizophrenia patients, 65 first-degree non-psychotic relatives of schizophrenia patients, 27 community comparison (CC) probands and 73 CC relatives were examined using tensor-based morphometry (TBM) to isolate global and localized differences in tissue volume across the entire brain between groups. We found brain tissue contractions most prominently in frontal and temporal regions and expansions in the putamen/ pallidum, and lateral and third ventricles in schizophrenia patients when compared to unrelated CC probands. Results were similar, though less prominent when patients were compared with their non-psychotic relatives. Structural deformations observed in unaffected patient relatives compared to age-similar CC relatives were suggestive of schizophrenia-related genetic liability and were pronounced in the putamen/ pallidum and medial temporal regions. Schizophrenia and genetic liability effects for the putamen/ pallidum were confirmed by regions-of-interest analysis. In conclusion, TBM findings complement reports of frontal, temporal and ventricular dysmorphology in schizophrenia and further indicate that putamen/ pallidum enlargements, originally linked mainly with medication exposure in early studies, also reflect a genetic predisposition for schizophrenia. Thus, brain deformation profiles revealed in this study may help to clarify the role of specific genetic or environmental risk factors towards altered brain morphology in schizophrenia.
Aberrant sensitivity of incentive neurocircuitry to nondrug rewards has been suggested as either a risk factor for or consequence of drug addiction. Using functional magnetic resonance imaging, we tested whether alcohol-dependent patients (ADP: n = 29) showed altered recruitment of ventral striatal (VS) incentive neurocircuitry compared to controls (n = 23) by: 1) cues to respond for monetary rewards, 2) post-response anticipation of rewards, or 3) delivery of rewards. Using an instrumental task with two-stage presentation of reward-predictive information, subjects saw cues signaling opportunities to win $0, $1, or $10 for responding to a target. Following this response, subjects were notified whether their success would be indicated by a lexical notification (“Hit?”) or by delivery of a monetary reward (“Win?”). After a variable interval, subjects then viewed the trial outcome. We found no significant group differences in voxelwise activation by task contrasts, or in signal change extracted from VS. Both ADP and controls showed significant VS and other limbic recruitment by pre-response reward anticipation. In addition, controls also showed VS recruitment by post-response reward-anticipation, and ADP had appreciable subthreshold VS activation. Both groups also showed similar mesolimbic responses to reward deliveries. Across all subjects, a questionnaire measure of “hot” impulsivity correlated with VS recruitment by post-response anticipation of low rewards and with VS recruitment by delivery of low rewards. These findings indicate that incentive-motivational processing of nondrug rewards is substantially maintained in recovering alcoholics, and that reward-elicited VS recruitment correlates more with individual differences in trait impulsivity irrespective of addiction.
Reward; Impulsivity; Nucleus accumbens; Ventral Striatum; Alcoholism; Substance use disorder; Instrumental behavior
Although obesity has been linked to structural brain changes, little is known about its associations with the rates of brain atrophy. We examined associations between global (BMI) and central (waist circumference) midlife obesity and subsequent trajectories of regional brain atrophy in 152 individuals (M (age) = 69±7.8) prospectively followed through the Baltimore Longitudinal Study of Aging; 21 individuals became impaired during follow-up. We report no associations (P’s > 0.05) between either global or central midlife obesity and subsequent rates of regional brain volume changes against a background of age-related atrophy in older individuals who remained non-demented. When looking at the entire sample, greater decline was observed in the volume of gray matter, precuneus, cingulate and orbito-frontal gyri for globally obese (P’s < 0.03), even though only data up to the point of dementia diagnosis were included in the analyses (i.e., while still considered clinically normal). Moreover, when trajectories of regional volume changes were examined across the range of BMI and waist circumference values instead of employing a cut-off point to define obesity, a different pattern of results emerged. Overall, our results suggest that midlife obesity may be an important modifier of brain atrophy in individuals who are developing cognitive impairment and dementia, while it has little effect on structural brain integrity in non-demented older adults. Moreover, the discrepancies in findings between studies may be in part due to participant sampling and methodological differences.
BMI; waist circumference; MRI; normal aging; MCI
One of the main obstacles in quantitative interpretation of functional magnetic resonance imaging (fMRI) signal is that this signal is influenced by non-neural factors such as vascular properties of the brain, which effectively increases signal variability. One approach to account for non-neural components is to identify and measure these confounding factors and to include them as covariates in data analysis or interpretation. Previously, several research groups have independently identified four potential physiologic modulators of fMRI signals, including baseline venous oxygenation (Yv), cerebrovascular reactivity (CVR), resting state BOLD fluctuation amplitude (RSFA), and baseline cerebral blood flow (CBF). This study sought to directly compare the modulation effects of these indices in the same fMRI session. The physiologic parameters were measured with techniques comparable with those used in the previous studies except for CBF, which was determined globally with a velocity-based phase-contrast MRI (instead of arterial-spin-labeling MRI). Using an event-related, scene-categorization fMRI task, we showed that the fMRI signal amplitude was positively correlated with CVR (P < 0.0001) and RSFA (P = 0.002), while negatively correlated with baseline Yv (P < 0.0001). The fMRI-CBF correlation did not reach significance, although the (negative) sign of the correlation was consistent with the earlier study. Furthermore, among the physiologic modulators themselves, significant correlations were observed between baseline Yv and baseline CBF (P = 0.01), and between CVR and RSFA (P = 0.05), suggesting that some of the modulators may partly be of similar physiologic origins. These observations as well as findings in recent literature suggest that additional measurement of physiologic modulator(s) in an fMRI session may provide a practical approach to control for inter-subject variations and to improve the ability of fMRI in detecting disease or medication related differences.
BOLD fMRI; normalization; venous oxygenation; cerebrovascular reactivity; resting state BOLD fluctuation; cerebral blood flow
Prenatal alcohol exposure (PAE) is associated with various adverse effects on human brain and behavior. Recently, neuroimaging studies have begun to identify PAE effects on specific brain structures. Investigation of such specific PAE effects is important for understanding the teratogenic mechanism of PAE on human brain, which is critical for differentiating PAE from other disorders. In this structural MRI study with young adults, PAE effects on the volumes of automatically segmented cortical and sub-cortical regions of interest (ROIs) were evaluated both through a group difference approach and a parametric approach. In the group difference approach (comparing among two PAE and a control groups), a disproportionate PAE effect was found in several occipital and temporal regions. This result is inconsistent with previous studies with child samples. Moreover, a gender difference in PAE effect was shown in some cortical ROIs. These findings suggest that sampling and gender may be important factors for interpreting specific PAE effects on human brain. With the parametric approach, it was demonstrated that the higher the PAE level, the smaller the entire brain, the lower the IQ. Several cortical and sub-cortical ROIs also exhibited a negative correlation between the PAE level and ROI volume. Furthermore, our data showed that the PAE effect on the brain could not be interpreted by the PAE effect on general physical growth until the young adult age. This study provides valuable insight into specific effects of PAE on human brain, and suggests important implications for future studies in this field.
prenatal alcohol exposure; structural MRI; brain segmentation; volume
Functional neuroanatomy of executive functions has been delineated in a large number of neuroimaging studies using conflict-inducing tasks. The neural basis of alcohol’s effects on cognitive control is poorly understood despite the evidence of impaired ability to evaluate competing demands and to inhibit maladaptive responses. In order to investigate effects of moderate intoxication, healthy social drinkers participated in both alcohol (0.60 g/kg ethanol for men, 0.55 g/kg for women) and placebo conditions while being scanned using blood oxygen level dependent (BOLD) fMRI. A modified 4-color Stroop task combined reading and color naming and used manual responses. Twenty subjects (10 women) were instructed to press a button corresponding to the font color except when a word was written in gray in which case they had to respond to the meaning of the word. Alcohol increased reaction times and a tendency to make more errors on incongruent trials. Behavioral indices of alcohol-induced premature responding correlated with the current drinking levels and impulsivity traits, suggesting an interaction between alcohol effects and personality predispositions. A distributed fronto-parietal cortical network was activated by incongruity. However, moderate alcohol inebriation selectively attenuated anterior cingulate cortex (ACC) activation during both high-conflict trials and erroneous responses, indicating vulnerability of the regulative function subserved by the ACC. By disrupting top-down, strategic processing, alcohol may interfere with goal-directed behavior, resulting in poor self control. The present results support models proposing that alcohol-induced prefrontal impairments diminish inhibitory control and are modulated by dispositional risk factors and levels of alcohol consumption.
cognitive control; anterior cingulate; error-related activity