Bradley G. Goodyear

Cue-Induced Brain Activity in Pathological Gamblers

BACKGROUND Previous studies using functional magnetic resonance imaging (fMRI) have identified differential brain activity in healthy subjects performing gambling tasks and in pathological gambling (PG) subjects when exposed to motivational and emotional predecessors for gambling as well as during gambling or response inhibition tasks. The goal of the present study was to determine if PG subjects exhibit differential brain activity when exposed to visual gambling cues. METHODS Ten male DSM-IV-TR PG subjects and 10 matched healthy control subjects underwent fMRI during visual presentations of gambling-related video alternating with video of nature scenes. RESULTS Pathological gambling subjects and control subjects exhibited overlap in areas of brain activity in response to the visual gambling cues; however, compared with control subjects, PG subjects exhibited significantly greater activity in the right dorsolateral prefrontal cortex (DLPFC), including the inferior and medial frontal gyri, the right parahippocampal gyrus, and left occipital cortex, including the fusiform gyrus. Pathological gambling subjects also reported a significant increase in mean craving for gambling after the study. Post hoc analyses revealed a dissociation in visual processing stream (dorsal vs. ventral) activation by subject group and cue type. CONCLUSIONS These findings may represent a component of cue-induced craving for gambling or conditioned behavior that could underlie pathological gambling.

Magnetic resonance imaging at 3.0 Tesla: challenges and advantages in clinical neurological imaging.

MR imaging at very high field (3.0 T) is a significant new clinical tool in the modern neuroradiological armamentarium. In this report, we summarize our 40-month experience in performing clinical neuroradiological examinations at 3.0 T and review the relevant technical issues. We report on these issues and, where appropriate, their solutions. Issues examined include: increased SNR, larger chemical shifts, additional problems associated with installation of these scanners, challenges in designing and obtaining appropriate clinical imaging coils, greater acoustic noise, increased power deposition, changes in relaxation rates and susceptibility effects, and issues surrounding the safety and compatibility of implanted devices. Some of the these technical factors are advantageous (eg, increased signal-to-noise ratio), some are detrimental (eg, installation, coil design and development, acoustic noise, power deposition, device compatibility, and safety), and a few have both benefits and disadvantages (eg, changes in relaxation, chemical shift, and susceptibility). Fortunately solutions have been developed or are currently under development, by us and by others, for nearly all of these challenges. A short series of 1.5 T and 3.0 T patient images are also presented to illustrate the potential diagnostic benefits of scanning at higher field strengths. In summary, by paying appropriate attention to the discussed technical issues, high-quality neuro-imaging of patients is possible at 3.0 T.

Neurovascular decoupling is associated with severity of cerebral amyloid angiopathy

Objectives: We used functional MRI (fMRI), transcranial Doppler ultrasound, and visual evoked potentials (VEPs) to determine the nature of blood flow responses to functional brain activity and carbon dioxide (CO2) inhalation in patients with cerebral amyloid angiopathy (CAA), and their association with markers of CAA severity. Methods: In a cross-sectional prospective cohort study, fMRI, transcranial Doppler ultrasound CO2 reactivity, and VEP data were compared between 18 patients with probable CAA (by Boston criteria) and 18 healthy controls, matched by sex and age. Functional MRI consisted of a visual task (viewing an alternating checkerboard pattern) and a motor task (tapping the fingers of the dominant hand). Results: Patients with CAA had lower amplitude of the fMRI response in visual cortex compared with controls (p = 0.01), but not in motor cortex (p = 0.22). In patients with CAA, lower visual cortex fMRI amplitude correlated with higher white matter lesion volume (r = −0.66, p = 0.003) and more microbleeds (r = −0.78, p < 0.001). VEP P100 amplitudes, however, did not differ between CAA and controls (p = 0.45). There were trends toward reduced CO2 reactivity in the middle cerebral artery (p = 0.10) and posterior cerebral artery (p = 0.08). Conclusions: Impaired blood flow responses in CAA are more evident using a task to activate the occipital lobe than the frontal lobe, consistent with the gradient of increasing vascular amyloid severity from frontal to occipital lobe seen in pathologic studies. Reduced fMRI responses in CAA are caused, at least partly, by impaired vascular reactivity, and are strongly correlated with other neuroimaging markers of CAA severity.

Neural Correlates of Concreteness in Semantic Categorization

In some contexts, concrete words (CARROT) are recognized and remembered more readily than abstract words (TRUTH). This concreteness effect has historically been explained by two theories of semantic representation: dual-coding [Paivio, A. Dual coding theory: Retrospect and current status. Canadian Journal of Psychology, 45, 255287, 1991] and context-availability [Schwanenflugel, P. J. Why are abstract concepts hard to understand? In P. J. Schwanenflugel (Ed.), The psychology of word meanings (pp. 223250). Hillsdale, NJ: Erlbaum, 1991]. Past efforts to adjudicate between these theories using functional magnetic resonance imaging have produced mixed results. Using event-related functional magnetic resonance imaging, we reexamined this issue with a semantic categorization task that allowed for uniform semantic judgments of concrete and abstract words. The participants were 20 healthy adults. Functional analyses contrasted activation associated with concrete and abstract meanings of ambiguous and unambiguous words. Results showed that for both ambiguous and unambiguous words, abstract meanings were associated with more widespread cortical activation than concrete meanings in numerous regions associated with semantic processing, including temporal, parietal, and frontal cortices. These results are inconsistent with both dual-coding and context-availability theories, as these theories propose that the representations of abstract concepts are relatively impoverished. Our results suggest, instead, that semantic retrieval of abstract concepts involves a network of association areas. We argue that this finding is compatible with a theory of semantic representation such as Barsalous [Barsalou, L. W. Perceptual symbol systems. Behavioral & Brain Sciences, 22, 577660, 1999] perceptual symbol systems, whereby concrete and abstract concepts are represented by similar mechanisms but with differences in focal content.

Functional connectivity of neural motor networks is disrupted in children with developmental coordination disorder and attention-deficit / hyperactivity disorder

Developmental coordination disorder (DCD) and attention deficit/hyperactivity disorder (ADHD) are prevalent childhood disorders that frequently co-occur. Evidence from neuroimaging research suggests that children with these disorders exhibit disruptions in motor circuitry, which could account for the high rate of co-occurrence. The primary objective of this study was to investigate the functional connections of the motor network in children with DCD and/or ADHD compared to typically developing controls, with the aim of identifying common neurophysiological substrates. Resting-state fMRI was performed on seven children with DCD, 21 with ADHD, 18 with DCD + ADHD and 23 controls. Resting-state connectivity of the primary motor cortex was compared between each group and controls, using age as a co-factor. Relative to controls, children with DCD and/or ADHD exhibited similar reductions in functional connectivity between the primary motor cortex and the bilateral inferior frontal gyri, right supramarginal gyrus, angular gyri, insular cortices, amygdala, putamen, and pallidum. In addition, children with DCD and/or ADHD exhibited different age-related patterns of connectivity, compared to controls. These findings suggest that children with DCD and/or ADHD exhibit disruptions in motor circuitry, which may contribute to problems with motor functioning and attention. Our results support the existence of common neurophysiological substrates underlying both motor and attention problems.

Simultaneous 3-T fMRI and high-density recording of human auditory evoked potentials.

We acquired simultaneous high-field (3 T) functional magnetic resonance imaging (fMRI) and high-density (64- and 128-channel) EEG using a sparse sampling technique to measure auditory cortical activity generated by right ear stimulus presentation. Using dipole source localization, we showed that the anatomical location of the grand mean equivalent dipole of auditory evoked potentials (AEPs) and the center of gravity of fMRI activity were in good agreement in the horizontal plane. However, the grand mean equivalent dipole was located significantly superior in the cortex compared to fMRI activity. Interhemispheric asymmetry was exhibited by fMRI, whereas neither the AEP dipole moments nor the mean global field power (MGFP) of the AEPs showed significant asymmetry. Increasing the number of recording electrodes from 64 to 128 improved the accuracy of the equivalent dipole source localization but decreased the signal-to-noise ratio (SNR) of MR images. This suggests that 64 electrodes may be optimal for use in simultaneous recording of EEG and fMRI.

Longitudinal Evaluation of Resting-State fMRI After Acute Stroke With Hemiparesis

Background. Functional magnetic resonance imaging (fMRI) of motor impairment after stroke strongly depends on patient effort and capacity to make a movement. Hence fMRI has had limited use in clinical management. Alternatively, resting-state fMRI (ie, with no task) can elucidate the brain’s functional connections by determining temporal synchrony between brain regions. Objective. The authors examined whether resting-state fMRI can elucidate the disruption of functional connections within hours of ischemic stroke as well as during recovery. Methods. A total of 51 ischemic stroke patients—31 with mild-to-moderate hand deficits (National Institutes of Health Stroke Scale [NIHSS] motor score ≥1) and 20 with NIHSS score of 0—underwent resting-state fMRI at <24 hours, 7 days, and 90 days poststroke; 15 age-matched healthy individuals participated in 1 session. Using the resting-state fMRI signal from the ipsilesional motor cortex, the strength of functional connections with the contralesional motor cortex was computed. Whole-brain maps of the resting-state motor network were also generated and compared between groups and sessions. Results. Within hours poststroke, patients with motor deficits exhibited significantly lower connectivity than controls (P = .02) and patients with no motor impairment (P = .03). Connectivity was reestablished after 7 days in recovered (ie, NIHSS score = 0) participants. After 90 days, recovered patients exhibited normal motor connectivity; however, reduced connectivity with subcortical regions associated with effort and cognitive processing remained. Conclusion. Resting-state fMRI within hours of ischemic stroke can demonstrate the impact of stroke on functional connections throughout the brain. This tool has the potential to help select appropriate stroke therapies in an acute imaging setting and to monitor the efficacy of rehabilitation.

Reduced Intrinsic Connectivity of Amygdala in Adults with Major Depressive Disorder

Imaging studies of major depressive disorder (MDD) have demonstrated enhanced resting-state activity of the amygdala as well as exaggerated reactivity to negative emotional stimuli relative to healthy controls (HCs). However, the abnormalities in the intrinsic connectivity of the amygdala in MDD still remain unclear. As the resting-state activity and functional connectivity (RSFC) reflect fundamental brain processes, we compared the RSFC of the amygdala between unmedicated MDD patients and HCs. Seventy-four subjects, 55 adults meeting the DSM-IV criteria for MDD and 19 HCs, underwent a resting-state 3-T functional magnetic resonance imaging scan. An amygdala seed-based low frequency RSFC map for the whole brain was generated for each group. Compared with HCs, MDD patients showed a wide-spread reduction in the intrinsic connectivity of the amygdala with a variety of brain regions involved in emotional processing and regulation, including the ventrolateral prefrontal cortex, insula, caudate, middle and superior temporal regions, occipital cortex, and cerebellum, as well as increased connectivity with the bilateral temporal poles (p < 0.05 corrected). The increase in the intrinsic connectivity of amygdala with the temporal poles was inversely correlated with symptom severity and anxiety scores. Although the directionality of connections between regions cannot be inferred from temporal correlations, the reduced intrinsic connectivity of the amygdala predominantly with regions involved in emotional processing may reflect impaired bottom-up signaling for top-down cortical modulation of limbic regions leading to abnormal affect regulation in MDD.

Neural Correlates of Pathological Gamblers Preference for Immediate Rewards During the Iowa Gambling Task: An fMRI Study

The Iowa Gambling Task (IGT) involves exploratory learning via rewards and penalties, where most advantageous task performance requires subjects to forego potential large immediate rewards for small longer-term rewards to avoid larger punishments. Pathological gambling (PG) subjects perform worse on the IGT compared to controls, relating to their persistence at high risk decisions involving the continued choice of potential large immediate rewards despite experiencing larger punishments. We wished to determine if neural processing of risk and reward within striatal and frontal cortex is associated with this behaviour observed in PG. Functional magnetic resonance imaging (fMRI) was used to assess brain activity in response to a computerized version of the IGT. Thirteen male PG subjects with no active comorbidities were compared to 13 demographically matched control subjects. In agreement with previous behavioural studies, PG subjects performed worse on the IGT and made more high-risk choices compared to controls, particularly after experiencing wins and losses. During high-risk gambling decisions, fMRI demonstrated that PG subjects exhibited relatively increased frontal lobe and basal ganglia activation, particularly involving the orbitofrontal cortex (OFC), caudate and amygdala. Increased activation of regions encompassing the extended reward pathway in PG subjects during high risk choices suggests that the persistence of PG may be due to the increased salience of immediate and greater potential monetary rewards relative to lower monetary rewards or potential future losses. Whether this over activation of the reward pathway is associated with the development of PG warrants further investigation.

The Neural Consequences of Semantic Richness When More Comes to Mind, Less Activation Is Observed

Some concepts have richer semantic representations than others. That is, when considering the meaning of concepts, subjects generate more information (more features, more associates) for some concepts than for others. This variability in semantic richness influences responses in speeded tasks that involve semantic processing, such as lexical decision and semantic categorization tasks. It has been suggested that concepts with richer semantic representations build stronger attractors in semantic space, allowing faster settling of activation patterns and thus faster responding. Using event-related functional magnetic resonance imaging, we examined the neural activation associated with semantic richness by contrasting activation for words with high and low numbers of associates in a semantic categorization task. Results were consistent with faster semantic settling for words with richer representations: Words with a low number of semantic associates produced more activation than words with a high number of semantic associates in a number of regions, including left inferior frontal and inferior temporal gyri.