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Langguth et al. (2006) described a method for targeting primary auditory cortex (PAC) during transcranial magnetic stimulation (TMS) using the 10–20 electroencephalography system. Study aims were to measure the degree of accuracy in placing the TMS coil on the scalp overlying PAC using the 10–20 method and determine the extent to which accuracy depends on the hemisphere of the coil placement. Twelve participants underwent anatomical magnetic resonance imaging (MRI) of their head in a 3T scanner. Before imaging, a fiducial marker was placed on their scalp corresponding to the TMS coil position. MRI scans were analyzed to determine the distance from the fiducial marker to PAC for each participant. On average, the 10–20 method resulted in distances in the medial–lateral, anterior-posterior, and inferior-superior dimensions that were within a few millimeters (~ 4 mm) of each other between the left and right hemispheres. The fiducial marker was, on average, 10.4 mm superior and 10.8 mm posterior to the optimal scalp location that minimized the distance to PAC. Individual asymmetries and other systematic differences found in this study raise important considerations to keep in mind that might necessitate using an MRI-guided method of coil-positioning when targeting PAC for TMS.

Current research in connectomics highlights that self-organized functional networks or "communities" of cortical areas can be detected in the adult brain. This perspective may provide clues to mechanisms of treatment response in psychiatric conditions. Here we examine functional brain community topology based on resting-state fMRI in adult Attention-Deficit/Hyperactivity Disorder (ADHD; n = 22) and controls (n = 31). We sought to evaluate ADHD patterns in adulthood and their modification by short term stimulants administration. Participants with ADHD were scanned one or two weeks apart, once with medication and once without; comparison participants were scanned at one time-point. Functional connectivity was estimated from these scans and community detection applied to determine cortical network topology. Measures of change in connectivity profile were calculated via a graph measure, termed the Node Dissociation Index (NDI). Compared to controls, several cortical networks had atypical connectivity in adults with ADHD when withholding stimulants, as measured by NDI. In most networks stimulants significantly reduced, but did not eliminate, differences in the distribution of connections between key brain systems relative to the control sample. These findings provide an enriched model of connectivity in ADHD and demonstrate how stimulants may exert functional effects by altering connectivity profiles in the brain.

Background Neural correlates of stress regulation via the hypothalamic-pituitary-adrenal (HPA) axis have been identified, but little is known about how these apply to real-world interpersonal stress contexts such as mother-infant interaction. We extended stress regulation research by examining maternal neural activation to infant cry related to HPA regulation with their infants. Methods Twenty-two primiparous mothers listened to the cry sounds of their own 18-month-old infant and an unfamiliar infant and a control sound during functional magnetic resonance imaging scanning. Salivary cortisol was collected at four timepoints in a separate session involving the Strange Situation stressor. Cortisol trajectories were modeled with hierarchical linear modeling, and trajectory terms were used to predict neural response to own infant cry. Results Mothers who showed less HPA reactivity—indexed by trajectory curvature rather than level—showed increased activation to the cry of their infant relative to control sound across limbic/paralimbic and prefrontal circuits. These included periaqueductal gray, right insula, and bilateral orbitofrontal cortex as well as anterior cingulate-medial prefrontal cortex. Activations overlapped to some extent with previous HPA regulation findings and converged more extensively with circuits identified in other maternal response paradigms. Conclusions Maternal stress regulation involves both circuits found across stressor types (i.e., prefrontal) and areas unique to the mother-infant relationship (i.e., limbic/paralimbic). The shape of the HPA response trajectory of mothers was more important than the level of such response in defining stress-related neural correlates. Future research should consider dimensions of the stress context and of physiological trajectories to define stress-regulatory circuits.

Several recent studies have documented age-related changes in brain activity—less amygdala activity and higher prefrontal activity in response to emotional stimuli. Using functional magnetic resonance imaging (fMRI), we examined whether aging also affects the maintenance of activity to emotional stimuli and whether maintenance differs by the valence (negative, neutral and positive) of the pictures. Younger participants had a larger volume of activity in the amygdala but less in the prefrontal cortex than the old. The old showed more habituation to highly arousing negative but not positive or neutral stimuli in prefrontal cortex as compared to younger participants. Thus prefrontal cortex activity indexes emotion in the elderly, but not the young. Amplified prefrontal activity suggests elderly increase cognitive control for negative, highly arousing emotional stimuli, but it is not maintained. Taken together, age-related increases in prefrontal activity and reduced amygdala activity may underlie observed affective changes in aging.

Teenagers are often impulsive. In some cases this is a phase of normal development; in other cases impulsivity contributes to criminal behavior. Using functional magnetic resonance imaging, we examined resting-state functional connectivity among brain systems and behavioral measures of impulsivity in 107 juveniles incarcerated in a high-security facility. In less-impulsive juveniles and normal controls, motor planning regions were correlated with brain networks associated with spatial attention and executive control. In more-impulsive juveniles, these same regions correlated with the default-mode network, a constellation of brain areas associated with spontaneous, unconstrained, self-referential cognition. The strength of these brain–behavior relationships was sufficient to predict impulsivity scores at the individual level. Our data suggest that increased functional connectivity of motor-planning regions with networks subserving unconstrained, self-referential cognition, rather than those subserving executive control, heightens the predisposition to impulsive behavior in juvenile offenders. To further explore the relationship between impulsivity and neural development, we studied functional connectivity in the same motor-planning regions in 95 typically developing individuals across a wide age span. The change in functional connectivity with age mirrored that of impulsivity: younger subjects tended to exhibit functional connectivity similar to the more-impulsive incarcerated juveniles, whereas older subjects exhibited a less-impulsive pattern. This observation suggests that impulsivity in the offender population is a consequence of a delay in typical development, rather than a distinct abnormality.

Early onset blindness leads to a dramatic alteration in the way the world is perceived, a change that is detectable in the organization of the brain. Several studies have confirmed that blindness leads to functional alterations in occipital cortices that normally serve visual functions. These reorganized brain regions respond to a variety of tasks and stimuli, but their specific functions are unclear. In sighted individuals, several studies have reported preparatory activity in retinotopic areas, which enhances perceptual sensitivity. “Baseline shifts,” changes in activity associated with a cue predicting an upcoming event, provides a marker for attentional modulation. Here we demonstrate that, in early blind subjects, medial occipital areas produced significant blood oxygenation level-dependent (BOLD) responses to a cue signaling an auditory discrimination trial but not to a cue indicating a no-trial period. Furthermore, the amplitude of the BOLD response in the anterior calcarine sulcus of early blind subjects correlated with their discrimination performance on the auditory backward masking task. Preparatory BOLD responses also were present in auditory cortices, although they were more robust in blind than sighted control subjects. The pattern of response in visual areas is similar to preparatory effects observed during visual selective attention in sighted subjects and consistent with the hypothesis that the mechanisms implicated in visual attention continue to modulate occipital cortex in the early blind. A possible source of this top-down modulation may be the frontoparietal circuits that retain their connectivity with the reorganized occipital cortex and as a result influence processing of nonvisual stimuli in the blind.

Objective Ferumoxytol, an iron oxide nanoparticle that targets phagocytic cells, can be used in magnetic resonance imaging of malignant brain tumors and can be administered as a bolus, allowing dynamic imaging. Our objectives were to determine the optimum time of delayed contrast enhancement of ferumoxytol, and to compare ferumoxytol and gadolinium contrast agents for magnetic resonance angiography and perfusion. Methods Twelve patients with malignant brain tumors underwent serial magnetic resonance imaging multiple times up to 72 hours after ferumoxytol injection at both 1.5 and 3-T. The enhancement time course was determined for ferumoxytol and compared with a baseline gadolinium scan. Perfusion, time-of-flight and dynamic magnetic resonance angiography and T1-weighted scans were compared for the two agents. Results The lesions were detectable at all field strengths, even with an intraoperative 0.15-T magnet. Maximal ferumoxytol enhancement intensity was at 24 to 28 hours after administration, and the enhancing volume subsequently expanded with time into a non-gadolinium-enhancing, high T2-weighted signal region of tumor-infiltrated brain. Dynamic studies were assessed with both agents, indicating early vascular leak with gadolinium but not with ferumoxytol. Conclusion Our most important finding was that gadolinium leaks out of blood vessels early after injection, whereas ferumoxytol stays intravascular in the "early" phase, thereby increasing the accuracy of tumor perfusion assessment. As a magnetic resonance imaging contrast agent, ferumoxytol visualizes brain tumors at all field strengths evaluated, with delayed enhancement peaking at 24 to 28 hours after administration.

For blind individuals, audition provides critical information for interacting with the environment. Individuals blinded early in life (EB) typically show enhanced auditory abilities relative to sighted controls as measured by tasks requiring complex discrimination, attention and memory. In contrast, few deficits have been reported on tasks involving auditory sensory thresholds (e.g., Yates, J.T., Johnson, R.M., Starz, W.J., 1972. Loudness perception of the blind. Audiology 11(5), 368-376; Starlinger, I., Niemeyer, W., 1981. Do the blind hear better? Investigations on auditory processing in congenital or early acquired blindness. I. Peripheral functions. Audiology 20(6), 503-509). A study of gap detection stands at odds with this distinction [Muchnik, C., Efrati, M., Nemeth, E., Malin, M., Hildesheimer, M., 1991. Central auditory skills in blind and sighted subjects. Scand. Audiol. 20(1), 19-23]. In the current investigation we re-examined gap detection abilities in the EB using a single-interval, yes/no method. A group of younger sighted control individuals (SCy) was included in the analysis in addition to EB and sighted age matched control individuals (SCm) in order to examine the effect of age on gap detection performance. Estimates of gap detection thresholds for EB subjects were nearly identical to SCm subjects and slightly poorer relative to the SCy subjects. These results suggest some limits on the extent of auditory temporal advantages in the EB.

Human speech carries both linguistic content and information about the speaker's identity and affect. While neuroimaging has been used extensively to study verbal memory, there has been little attention to the neural basis of memory for voices. Evidence from studies of aphasia and auditory agnosia suggests that voice memory may rely on anatomically distinct areas in the right temporal and parietal lobes regions, but there is little data on the broader neural systems involved in voice memory. The present study tested the hypothesis that the neural systems involved in voice memory are functionally distinct from the systems involved in word recognition and are primarily located in the right cerebral hemisphere. Subjects performed two-back tasks in which they were required to alternately remember the voices speaking (Voice condition), and the words they produced (Word condition). A tone memory condition was also included, as a non-speech comparison. The contrast between the Voice and Word conditions revealed greater Voice-related effects in left temporal, right frontal and right medial parietal areas, while the Word-related effects appeared in left frontal and bilateral parietal areas. These findings map out a partially right-lateralized fronto-parietal network associated with voice memory, which can be distinguished from predominantly left-hemisphere regions associated with verbal working memory. These results provide further evidence that distinct neural systems are associated with the carrier waves of speech and word identity.

Functional magnetic resonance imaging (fMRI) was used to investigate the spatial distribution of cortical activation in frontal and parietal lobes during auditory and visual oddball tasks in 10 healthy subjects. The purpose of the study was to compare activation within auditory and visual modalities and identify common patterns of activation across these modalities. Each subject was scanned eight times, four times each for the auditory and visual conditions. The tasks consisted of a series of trials presented every 1500 ms of which 4-6% were target trials. Subjects kept a silent count of the number of targets detected during each scan. The data were analyzed by correlating the fMRI signal response of each pixel to a reference hemodynamic response function that modeled expected responses to each target stimulus. The auditory and visual targets produced target-related activation in frontal and parietal cortices with high spatial overlap particularly in the middle frontal gyrus and in the anterior cingulate. Similar convergence zones were detected in parietal cortex. Temporal differences were detected in the onset of the activation in frontal and parietal areas with an earlier onset in parietal areas than in the middle frontal areas. Based on consistent findings with previous event-related oddball tasks, the high degree of spatial overlap in frontal and parietal areas appears to be due to modality independent or amodal processes related to procedural aspects of the tasks that may involve memory updating and non-specific response organization.

Difficulty with selective attention is a frequent complaint of adult patients with ADHD, but selective attention tasks have not provided robust evidence of attentional dysfunction in this group. Two experiments examine this puzzle by distinguishing between failures of spatial selection and problems due to sensitivity to perceptual interference. In Experiment 1, we measured the level of perceptual interference generated by targets in crowded displays with nearby distractors by comparing luminance thresholds in both distractor-present (noise) and distractor-absent (clean) displays. ADHD and control participants had comparable thresholds for clean displays, but ADHD individuals had elevated thresholds to crowded displays. These effects could be explained in two distinct ways. Deficits may have arisen from amplified visual interference in the noise condition, or from abnormalities in top-down attentional processes that reduce visual interference. Experiment 2 adjusted for individual perceptual differences with clean and noise displays, before measuring visual interference resolution at attended versus unattended locations. ADHD and control groups had comparable interference resolution at attended locations. These results suggest that perceptual interference rather than spatial attention deficits may account for some deficits in ADHD. This putative deficit in sensory function highlights a potential early-stage perceptual processing deficit in ADHD distinct from selective attention.

Background Cognitive abilities, such as working memory, differ among people; however, individuals also vary in their own day-to-day cognitive performance. One potential source of cognitive variability may be fluctuations in the functional organization of neural systems. The degree to which the organization of these functional networks is optimized may relate to the effective cognitive functioning of the individual. Here we specifically examine how changes in the organization of large-scale networks measured via resting state functional connectivity MRI and graph theory track changes in working memory capacity. Methodology/Principal Findings Twenty-two participants performed a test of working memory capacity and then underwent resting-state fMRI. Seventeen subjects repeated the protocol three weeks later. We applied graph theoretic techniques to measure network organization on 34 brain regions of interest (ROI). Network modularity, which measures the level of integration and segregation across sub-networks, and small-worldness, which measures global network connection efficiency, both predicted individual differences in memory capacity; however, only modularity predicted intra-individual variation across the two sessions. Partial correlations controlling for the component of working memory that was stable across sessions revealed that modularity was almost entirely associated with the variability of working memory at each session. Analyses of specific sub-networks and individual circuits were unable to consistently account for working memory capacity variability. Conclusions/Significance The results suggest that the intrinsic functional organization of an a priori defined cognitive control network measured at rest provides substantial information about actual cognitive performance. The association of network modularity to the variability in an individual's working memory capacity suggests that the organization of this network into high connectivity within modules and sparse connections between modules may reflect effective signaling across brain regions, perhaps through the modulation of signal or the suppression of the propagation of noise.

Methamphetamine (MA)-dependent individuals prefer smaller immediate over larger delayed rewards in delay discounting (DD) tasks. Human and animal data implicate ventral (amygdala, ventral striatum, ventrolateral prefrontal cortex insula) and dorsal (dorsolateral prefrontal cortex, dorsal anterior cingulate cortex and posterior parietal cortex) systems in DD decisions. The ventral system is hypothesized to respond to the salience and immediacy of rewards while the dorsal system is implicated in the process of comparison and choice.We used functional Magnetic Resonance Imaging to probe the neural correlates of DD in 19 recently abstinent MA-dependent patients and 17 age- and gender-matched controls.Hard DD choices were associated with greatest activation in bilateral middle cingulate, posterior parietal cortex (PPC), and the right rostral insula. Control subjects showed more activation than MA patients bilaterally in the precuneus and in the right caudate nucleus, anterior cingulate cortex (ACC), and dorsolateral prefrontal cortex (DLPFC). Magnitude of discounting was correlated with activity in the amygdala, DLPFC, posterior cingulate cortex and PPC.Our findings were consistent with a model wherein dorsal cognitive systems modulate the neural response of ventral regions. Patients addicted to MA, who strongly prefer smaller immediate over larger delayed rewards, activate the dorsal cognitive control system in order to overcome their preference. Activation of the amygdala during choice of delayed rewards was associated with a greater degree of discounting, suggesting that heavily discounting MA-dependent individuals may be more responsive to the negative salience of delayed rewards than controls.

We used functional magnetic resonance imaging (fMRI) to examine responses within auditory cortical fields during the passive listening of pure tone (PT) and frequency modulated (FM) stimuli in seven early blind (EB), five late blind (LB) and six sighted control (SC) individuals. Subjects were scanned using a "sparse sampling" imaging technique while listening to PT and FM sounds presented at either low (400 Hz) or high (4 kHz) center frequencies. When high tones were directly compared to low tones, the resulting activation maps showed a general tonotopic organization within the superior and middle temporal lobes at statistically significant thresholds for the SC and LB groups while the EB group showed a comparable tonotopic organization but only at statistically non-significance thresholds. A contrast of all tonal stimuli to a quiet baseline similarly revealed significantly less signal volume in the EB than in either the LB or SC groups. These results suggest that EB does not alter inherent patterns of tonotopic organization but rather, under low-demand listening conditions, results in a more efficient processing of simple auditory stimuli within the early stages of the auditory hierarchy. While these effects must be interpreted cautiously due to the small sample sizes, they indicate that functional responses in auditory cortical areas are altered by visual deprivation and that intramodal auditory plasticity may underlie previously reported auditory advantages observed in the blind.

Self-report surveys and behavioral tasks indicate greater risk-taking behavior in adolescents as compared with adults. However, the underlying causes of these behavioral differences remain unclear. The present study examined the possibility that adolescents may be more susceptible to immediate positive and negative outcomes than adults. We compared the behavior of adolescents and adults on a modified version of the Balloon Analogue Risk Task (Lejuez et al., 2002). The task required that participants press a button to "inflate" a series of balloons on a computer screen. Balloons inflated until either the participant released the button ("saved" balloons) or the balloon "burst." Accumulated points increased as the duration of the buttonpress increased; however, simultaneously, the likelihood that the balloon would burst also increased. Adolescents inflated balloons to a larger size prior to saving them than adults did, suggesting relatively higher levels of risk taking, although the adolescents' behavior was not uniformly risk prone. Further, in comparison with adults, behavior in adolescents was more influenced by whether a balloon was saved or had burst on the preceding trial, suggesting that sensitivity to immediate consequences is one mechanism that underlies the observed difference in risk taking.

Visual deprivation early in life results in occipital cortical responsiveness across a broad range of perceptual and cognitive tasks. In the reorganized occipital cortex of early blind (EB) individuals, the relative lack of specificity for particular sensory stimuli and tasks suggests that attention effects may play a prominent role in these areas. We wished to establish whether occipital cortical areas in the EB were responsive to stimuli across sensory modalities (auditory, tactile) and whether these areas maintained or altered their activity as a function of selective attention. Using a three-stimulus oddball paradigm and event-related functional magnetic resonance imaging, auditory and tactile tasks presented separately demonstrated that several occipital regions of interest (ROIs) in the EB, but not sighted controls (SCs), responded to targets and task-irrelevant distracter stimuli of both modalities. When auditory and tactile stimuli were presented simultaneously with subjects alternating attention between sensory streams, only the calcarine sulcus continued to respond to stimuli in both modalities. In all other ROIs, responses to auditory targets were as large or larger than those observed in the auditory-alone condition, but responses to tactile targets were attenuated or abolished by the presence of unattended auditory stimuli. Both auditory and somatosensory cortices responded consistently to auditory and tactile targets, respectively. These results reveal mechanisms of orienting and selective attention within the visual cortex of EB individuals and suggest that mechanisms of enhancement and suppression interact asymmetrically on auditory and tactile streams during bimodal sensory presentation.

What happens in vision-related cortical areas when congenitally blind (CB) individuals orient attention to spatial locations? Previous neuroimaging of sighted individuals has found overlapping activation in a network of frontoparietal areas including frontal eye fields (FEF), during both overt (with eye movement) and covert (without eye movement) shifts of spatial attention. Since voluntary eye movement planning seems irrelevant in CB, their FEF neurons should be recruited for alternative functions if their attentional role in sighted individuals is only due to eye movement planning. Recent neuroimaging of the blind has also reported activation in medial occipital areas, normally associated with visual processing, during a diverse set of non-visual tasks, but their response to attentional shifts remains poorly understood. Here, we used event-related fMRI to explore FEF and medial occipital areas in CB individuals and sighted controls with eyes closed (SC) performing a covert attention orienting task with endogenous verbal cues and spatialized auditory targets. We found robust stimulus-locked FEF activation of all CB subjects, similar to and stronger than in SC, suggesting that FEF plays a role in endogenous orienting of covert spatial attention even in individuals in whom voluntary eye movements are irrelevant. We also found robust activation in bilateral medial occipital cortex in CB but not in SC subjects. The response decreased below baseline following endogenous verbal cues but increased following auditory targets, suggesting that the medial occipital area in CB does not directly engage during cued orienting of attention but may be recruited for processing of spatialized auditory targets.

Early-onset blindness (EB) produces measurable advantages in auditory perception, attention, memory and language. Neville and Bavelier [Neville, H. J., & Bavelier, D. (2001) Variability of developmental plasticity. In J. L. McClelland, R. S. Siegler (Eds.) Mechanisms of cognitive development: Behavioral and ellon symposia on cognition (pp. 271–301)] hypothesized that faster temporal processing underlies many auditory compensatory effects in the blind. We tested this hypothesis by comparing early-onset blind individuals and sighted counterparts (SC) by assessing their rates of perceptual consolidation, the accurate perceptual representation of auditory stimuli. Firstly, we first tested both groups on a temporal-order judgment task (TOJ). EB subjects had significantly lower TOJ thresholds than the SC subjects. Secondly, we assessed perceptual consolidation speed using auditory backward masking tasks, taking into account individual TOJ thresholds. Discrimination performance was unaffected at all mask delays in the EB group while the SC subjects needed a mask delay of 160 ms to perform comparably. A backward masking task using single tone stimuli found no differences between the EB and SC groups any mask delay. A simultaneous masking task demonstrated that the mask effectively impaired discrimination in EB subjects at sensory stages. These results suggest that advantages in perceptual consolidation may reflect a mechanism responsible for the short response times and better performance reported in early blind individuals across a number of complex auditory tasks.

Background Verbal learning and memory deficits are among the most severe cognitive deficits observed in schizophrenia. We have demonstrated that such deficits do not extend to working memory for tones in a substantial number of patients even when verbal working memory is impaired. In this study we used functional magnetic resonance imaging to study the neural basis of this dissociation of auditory verbal and nonverbal working memory in individuals with schizophrenia. Methods While undergoing functional magnetic resonance imaging, 12 schizophrenic patients and 12 matched control subjects performed auditory Word Serial Position Task and Tone Serial Position Task. Results Both tasks produced activation in frontal cortex and temporal and parietal lobes of the cerebrum in both groups. While robust activation was observed in the left inferior frontal gyrus (areas 6, 44, and 45) in the control group during the Word Serial Position Task, activation in the patient group was much reduced in these areas and failed to show the same task-specific activation as in controls. Reduced activation in patients was not confined to the inferior frontal gyrus, but also extended to a medial area during the Tone Serial Position Task and to premotor and anterior temporal lobe areas during both tasks. Conclusions These findings support the hypothesis that abnormalities in cortical hemodynamic response in the inferior frontal gyrus underlie the verbal working memory deficit in schizophrenia. The relationship of verbal working memory deficits to other cognitive functions suggests that abnormal functioning in the speech-related areas may reflect a critical substrate of a broad range of cognitive dysfunctions associated with schizophrenia.

Background Verbal memory deficits have been reported in many studies of patients with schizophrenia. We evaluated the specificity of these deficits by comparing patients and control subjects on several verbal and nonverbal auditory memory tests. Methods Performance of stable, medicated outpatients with DSM-III-R diagnoses of schizophrenia (N=38) was compared with that of healthy subjects (N=39) on a word list immediate recall task, tone delayed discrimination tasks, and word and tone serial position tasks. Before memory testing, patients were divided into 2 groups based on their ability to perform normally on a screening test requiring pitch discrimination and sustained attention. Results The nonverbal tests were more difficult for control subjects than the verbal tests. Despite this, patients who performed normally on the screening test of perception and attention performed normally on both nonverbal tests but had highly significant deficits on both verbal tests ( P P =.02). Patients who performed poorly on the screening test had highly significant performance deficits on all the memory tests. Conclusions One subgroup of patients with schizophrenia has a selective deficit in verbal memory despite normal motivation, attention, and general perceptual function. Another group has deficits in multiple aspects of cognitive function suggestive of failure in early stages of information processing.