The question of whether recognition memory judgments with and without recollection reflect dissociable patterns of brain activity is unresolved. We used event-related, functional magnetic resonance imaging (fMRI) of 12 healthy volunteers to measure hemodynamic responses associated with both studying and recognizing words. Volunteers made one of three judgments to each word during recognition: whether they recollected seeing it during study (R judgments), whether they experienced a feeling of familiarity in the absence of recollection (K judgments), or whether they did not remember seeing it during study (N judgments). Both R and K judgments for studied words were associated with enhanced responses in left prefrontal and left parietal cortices relative to N judgments for unstudied words. The opposite pattern was observed in bilateral temporoccipital regions and amygdalae. R judgments for studied words were associated with enhanced responses in anterior left prefrontal, left parietal, and posterior cingulate...

The blood oxygenation level-dependent (BOLD) signal serves as the basis for human functional MRI (fMRI). Knowledge of the properties of the BOLD signal, such as how linear its response is to sensory stimuli, is essential for the design and interpretation of fMRI experiments. Here, we combined the cell-type and site-specific causal control provided by optogenetics and fMRI (opto-fMRI) in mice to test the linearity of BOLD signals driven by locally induced excitatory activity. We employed high-resolution mouse fMRI at 9.4 tesla to measure the BOLD response, and extracellular electrophysiological recordings to measure the effects of stimulation on single unit, multiunit, and local field potential activity. Optically driven stimulation of layer V neocortical pyramidal neurons resulted in a positive local BOLD response at the stimulated site. Consistent with a linear transform model, this locally driven BOLD response summated in response to closely spaced trains of stimulation. These properties were equivalent ...

Adjustment of response threshold for speed compared with accuracy instructions in two-choice decision-making tasks is associated with activation in the fronto-striatal network, including the pre-supplementary motor area (pre-SMA) and striatum ([Forstmann et al., 2008][1]). In contrast, increased response conservativeness is associated with activation of the subthalamic nucleus (STN) ([Frank et al., 2007][2]). We investigated the involvement of these regions in trial-by-trial adjustments of response threshold in humans, using a cued-trials task-switching paradigm. Fully and partially informative switch cues produced more conservative thresholds than repeat cues. Repeat cues were associated with higher activation in pre-SMA and striatum than switch cues. For all cue types, individual variability in response threshold was associated with activation level in pre-SMA, with higher activation linked to lower threshold setting. In the striatum, this relationship was found for repeat cues only. These findings suppo...

Using noninvasive functional magnetic resonance imaging (fMRI) technique, we analyzed the responses in human area MT with regard to visual motion, color, and luminance contrast sensitivity, and retinotopy. As in previous PET studies, we found that area MT responded selectively to moving (compared to stationary) stimuli. The location of human MT in the present fMRI results is consistent with that of MT in earlier PET and anatomical studies. In addition we found that area MT has a much higher contrast sensitivity than that in several other areas, including primary visual cortex (V1). Functional MRI half- amplitudes in V1 and MT occurred at approximately 15% and 1% luminance contrast, respectively. High sensitivity to contrast and motion in MT have been closely associated with magnocellular stream specialization in nonhuman primates. Human psychophysics indicates that visual motion appears to diminish when moving color-varying stimuli are equated in luminance. Electrophysiological results from macaque MT sugg...

Information integration across different sensory modalities contributes to object recognition, the generation of associations and long-term memory representations. Here, we used functional magnetic resonance imaging adaptation to investigate the presence of sensory integrative effects at cortical levels as early as nonprimary auditory and extrastriate visual cortices, which are implicated in intermediate stages of object processing. Stimulation consisted of an adapting audiovisual stimulus S1 and a subsequent stimulus S2 from the same basic-level category (e.g., cat). The stimuli were carefully balanced with respect to stimulus complexity and semantic congruency and presented in four experimental conditions: (1) the same image and vocalization for S1 and S2, (2) the same image and a different vocalization, (3) different images and the same vocalization, or (4) different images and vocalizations. This two-by-two factorial design allowed us to assess the contributions of auditory and visual stimulus repetiti...

Absence seizures are 5–10 s episodes of impaired consciousness accompanied by 3–4 Hz generalized spike-and-wave discharge on electroencephalography (EEG). The time course of functional magnetic resonance imaging (fMRI) changes in absence seizures in relation to EEG and behavior is not known. We acquired simultaneous EEG–fMRI in 88 typical childhood absence seizures from nine pediatric patients. We investigated behavior concurrently using a continuous performance task or simpler repetitive tapping task. EEG time–frequency analysis revealed abrupt onset and end of 3–4 Hz spike-wave discharges with a mean duration of 6.6 s. Behavioral analysis also showed rapid onset and end of deficits associated with electrographic seizure start and end. In contrast, we observed small early fMRI increases in the orbital/medial frontal and medial/lateral parietal cortex >5 s before seizure onset, followed by profound fMRI decreases continuing >20 s after seizure end. This time course differed markedly from the hemodynamic re...

We designed phosphorothioate-modified DNA probes linked to superparamagnetic iron oxide nanoparticles (SPION) for in vivo magnetic resonance imaging (MRI) of fosB and ΔfosB mRNA after amphetamine (AMPH) exposure in mice. Specificity of both the fosB and ΔfosB probes was verified by in vitro reverse transcriptase-PCR amplification to a single fragment of total cDNA obtained from acutely AMPH-exposed mouse brains. We confirmed time-dependent uptake and retention profiles of both probes in neurons of GAD67-green fluorescent protein knock-in mice. MRI signal of SPION-labeled fosB probe delivered via intracerebroventricular route was elevated in both acutely and chronically AMPH-exposed mice; the signal was suppressed by dopaminergic receptor antagonist pretreatment. SPION-labeled ΔfosB probe signal elevation occurred only in chronically AMPH-exposed mice. The in vivo target specificity of these probes permits reliable MRI visualization of AMPH-induced differential elevations of fosB and ΔfosB mRNA in living br...

Using functional magnetic resonance imaging, we estimated neural activity in twins to study genetic influences on the cortical response to categories of visual stimuli (faces, places, and pseudowords) that are known to elicit distinct patterns of activity in ventral visual cortex. The neural activity patterns in monozygotic twins were significantly more similar than in dizygotic twins for the face and place stimuli, but there was no effect of zygosity for pseudowords (or chairs, a control category). These results demonstrate that genetics play a significant role in determining the cortical response to faces and places, but play a significantly smaller role (if any) in the response to orthographic stimuli.

Hormonal satiety signals secreted by the gut play a pivotal role in the physiological control of appetite. However, therapeutic exploitation of the gut–brain axis requires greater insight into the interaction of gut hormones with CNS circuits of appetite control. Using the manganese ion (Mn2+) as an activity-dependent magnetic resonance imaging (MRI) contrast agent, we showed an increase in signal intensity (SI) in key appetite-regulatory regions of the hypothalamus, including the arcuate, paraventricular, and ventromedial nuclei, after peripheral injection of the orexigenic peptide ghrelin. Conversely, administration of the anorexigenic hormone peptide YY3–36 caused a reduction in SI. In both cases, the changes in SI recorded in the hypothalamic arcuate nucleus preceded the effect of these peptides on food intake. Intravenous Mn2+ itself did not significantly alter ghrelin-mediated expression of the immediate early gene product c-Fos, nor did it cause abnormalities of behavior or metabolic parameters. We ...

Response anticipation and response conflict processes are supported by executive control. However, few neuroimaging studies have attempted to study the relationship between these two processes in the same experimental session. In this study, we isolated brain activity associated with response anticipation (after a cue to prepare vs relax) and with response conflict (responding to a target with incongruent vs congruent flankers) and examined the independence and interaction of brain networks supporting these processes using event-related potentials (ERPs) and functional magnetic resonance imaging. Response anticipation generated a contingent negative variation ERP that correlated with shorter reaction times, and was associated with activation of a thalamo-cortico-striatal network, as well as increased gamma band power in frontal and parietal regions, and decreased spectral power in theta, alpha, and beta bands in most regions. Response conflict was associated with increased activation in the anterior cingul...