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How does our brain understand the number five when it is written as an Arabic numeral, and when presented as five fingers held up? Four facets have been implicated in adult numerical processing: semantic, visual, manual, and phonological/verbal. Here, we ask how the brain represents each, using a combination of tasks and stimuli. We collected fMRI data from adult participants while they completed our novel "four number code" paradigm. In this paradigm, participants viewed one of two stimulus types to tap into the visual and manual number codes, respectively. Concurrently, they completed one of two tasks to tap into the semantic and phonological/verbal number codes, respectively. Classification analyses revealed that neural codes representing distinctions between the number comparison and phonological tasks were generalizable across format (e.g., Arabic numerals to hands) within intraparietal sulcus (IPS), angular gyrus, and precentral gyrus. Neural codes representing distinctions between formats were generalizable across tasks within visual areas such as fusiform gyrus and calcarine sulcus, as well as within IPS. Our results identify the neural facets of numerical processing within a single paradigm and suggest that IPS is sensitive to distinctions between semantic and phonological/verbal, as well as visual and manual, facets of number representations., (© 2022 Massachusetts Institute of Technology.)

Background: Despite the well-known clinical effects of midazolam and ketamine, including sedation and memory impairment, the neural mechanisms of these distinct drugs in humans are incompletely understood. The authors hypothesized that both drugs would decrease recollection memory, task-related brain activity, and long-range connectivity between components of the brain systems for memory encoding, pain processing, and fear learning., Methods: In this randomized within-subject crossover study of 26 healthy adults, the authors used behavioral measures and functional magnetic resonance imaging to study these two anesthetics, at sedative doses, in an experimental memory paradigm using periodic pain. The primary outcome, recollection memory performance, was quantified with d' (a difference of z scores between successful recognition versus false identifications). Secondary outcomes were familiarity memory performance, serial task response times, task-related brain responses, and underlying brain connectivity from 17 preselected anatomical seed regions. All measures were determined under saline and steady-state concentrations of the drugs., Results: Recollection memory was reduced under midazolam (median [95% CI], d' = 0.73 [0.43 to 1.02]) compared with saline (d' = 1.78 [1.61 to 1.96]) and ketamine (d' = 1.55 [1.12 to 1.97]; P < 0.0001). Task-related brain activity was detected under saline in areas involved in memory, pain, and fear, particularly the hippocampus, insula, and amygdala. Compared with saline, midazolam increased functional connectivity to 20 brain areas and decreased to 8, from seed regions in the precuneus, posterior cingulate, and left insula. Compared with saline, ketamine decreased connectivity to 17 brain areas and increased to 2, from 8 seed regions including the hippocampus, parahippocampus, amygdala, and anterior and primary somatosensory cortex., Conclusions: Painful stimulation during light sedation with midazolam, but not ketamine, can be accompanied by increased coherence in brain connectivity, even though details are less likely to be recollected as explicit memories., (Copyright © 2021, the American Society of Anesthesiologists. All Rights Reserved.)

Introduction: Adults can represent numerical information in nonsymbolic and symbolic formats and flexibly switch between the two. While some studies suggest a strong link between the two number representation systems (e.g., Piazza, Izard, Pinel, Le Bihan, & Dehaene, 2004 Neuron , 44(3), 547), other studies show evidence against the strong-link hypothesis (e.g., Lyons, Ansari, & Beilock, 2012 Journal of Experimental Psychology: General , 141(4), 635). This inconsistency could arise from the relation between task demands and the closeness of the link between the two number systems., Methods: We used a passive viewing task and event-related potentials (ERP) to examine the temporal dynamics of the implicit integration between the nonsymbolic and symbolic systems. We focused on two ERP components over posterior scalp sites that were found to be sensitive to numerical distances and ratio differences in both numerical formats: a negative component that peaks around 170 ms poststimulus (N1) and a positive component that peaks around 200 ms poststimulus (P2p). We examined adults' ( n  =   55) ERPs when they were passively viewing simultaneously presented dot quantities and Arabic numerals (i.e., nonsymbolic and symbolic numerical information) in the double-digit range. For each stimulus, the nonsymbolic and symbolic content either matched or mismatched in number. We also asked each participant to estimate dot quantities in a separate behavioral task and observed that they tended to underestimate the actual dot quantities, suggesting a need to adjust the match between nonsymbolic and symbolic information to reflect the perceived quantity of the nonsymbolic information., Results: Using this adjustment, participants showed greater N1 and P2p amplitudes when perceived dot quantities matched Arabic numerals than when there was a mismatch. However, no differences were found between the unadjusted match and mismatch conditions., Conclusion: Our findings suggest that adults rapidly integrate nonsymbolic and symbolic formats of double-digit numbers, but evidence of such integration is best observed when the perceived (rather than veridical) dot quantity is considered.

Quitting smoking is the single best change in behavior that smokers can make to improve their health and extend their lives. Although most smokers express a strong desire to stop using cigarettes, the vast majority of quit attempts end in relapse. Relapse is particularly likely when smokers encounter cigarette cues. A striking number of relapses occur very quickly, with many occurring within as little as 24h. Characterizing what distinguishes successful quit attempts from unsuccessful ones, particularly just after cessation is initiated, is a research priority. We addressed this significant issue by examining the association between functional connectivity during cigarette cue exposure and smoking behavior during the first 24h of a quit attempt. Functional MRI was used to measure brain activity during cue exposure in nicotine-deprived daily smokers during the first day of a quit attempt. Participants were then given the opportunity to smoke. Using data collected in two parent studies, we identified a subset of participants who chose to smoke and a matched subset who declined (n=38). Smokers who were able to resist smoking displayed significant functional connectivity between the left anterior insula and the dorsolateral prefrontal cortex, whereas there was no such connectivity for those who chose to smoke. Notably, there were no differences in mean levels of activation in brain regions of interest, underscoring the importance of assessing interregional connectivity when investigating the links between cue-related neural responses and overt behavior. To our knowledge, this is the first study to link patterns of functional connectivity and actual cigarette use during the pivotal first hours of attempt to change smoking behavior., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Feedback about our choices is a crucial part of how we gather information and learn from our environment. It provides key information about decision experiences that can be used to optimize future choices. However, our understanding of the processes through which feedback translates into improved decision-making is lacking. Using neuroimaging (fMRI) and cognitive models of decision-making and learning, we examined the influence of feedback on multiple aspects of decision processes across learning. Subjects learned correct choices to a set of 50 word pairs across eight repetitions of a concurrent discrimination task. Behavioral measures were then analyzed with both a drift-diffusion model and a reinforcement learning model. Parameter values from each were then used as fMRI regressors to identify regions whose activity fluctuates with specific cognitive processes described by the models. The patterns of intersecting neural effects across models support two main inferences about the influence of feedback on decision-making. First, frontal, anterior insular, fusiform, and caudate nucleus regions behave like performance monitors, reflecting errors in performance predictions that signal the need for changes in control over decision-making. Second, temporoparietal, supplementary motor, and putamen regions behave like mnemonic storage sites, reflecting differences in learned item values that inform optimal decision choices. As information about optimal choices is accrued, these neural systems dynamically adjust, likely shifting the burden of decision processing from controlled performance monitoring to bottom-up, stimulus-driven choice selection. Collectively, the results provide a detailed perspective on the fundamental ability to use past experiences to improve future decisions., Competing Interests: The authors declare no competing conflicts of interest., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The vast majority of attempts to quit smoking cigarettes are unsuccessful. Negative affect (NA) is one of the primary factors contributing to smoking relapse, in part because it interferes with psychological processes that are essential for self-regulation and coping. Converging evidence suggests that NA may be less of a problem for smokers with high relative to low dispositional self-control, but very little is known about the mechanisms that underlie this effect. We used functional magnetic resonance imaging to address this issue by examining the associations between trait self-control, state levels of NA and patterns of brain activation in nicotine-deprived smokers (n = 117) during the performance of a verbal n-back paradigm (a task requiring cognitive processes that support self-regulation). While the activation of several brain regions linked to executive control correlated positively and negatively with state NA and trait self-control, respectively, an interaction between these factors was identified in only one region: the ventromedial prefrontal cortex (vmPFC). We conclude that the functions supported by the vmPFC are an important source of variability in smokers' self-regulatory functioning and propose that the region may contribute to the use of implicit forms of self-control under demanding circumstances., (© The Author (2013). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.)

Many cigarette smokers appear to experience ambivalence about smoking, defined as the simultaneous co-occurrence of a strong desire to smoke and a strong wish to quit smoking. Research suggests that this ambivalence about smoking affects how smokers respond to cigarette-related stimuli, but many important questions remain about precisely how smoking ambivalence influences cognitive and affective processing during cigarette cue exposure. We used functional magnetic resonance imaging (fMRI) to address this knowledge gap by examining the relation between self-reported ambivalence about smoking and cue-reactivity in quitting-motivated smokers presented with an opportunity to smoke. Eighty-two quitting-motivated cigarette smokers completed a measure assessing their ambivalence about smoking. Subsequently, participants initiated an attempt to quit smoking and underwent an fMRI session, during which they were asked to hold and view a cigarette. Consistent with hypotheses, results indicated that self-reported smoking ambivalence was negatively correlated with cigarette-related activation in brain areas linked to reward-related processing, motivation, and attention (i.e., rostral anterior cingulate and medial prefrontal cortex, caudate nucleus, visual cortex). Self-reported ambivalence was not, however, correlated with activation in brain regions related to conflict processing. This pattern of results is discussed with respect to the process of change for those attempting to quit smoking., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Working memory is believed to play a central role in almost all domains of higher cognition, yet the specific mechanisms involved in working memory are still fiercely debated. We describe a neuroimaging experiment with functional magnetic resonance imaging (fMRI) and a companion behavioral experiment, and in both we seek to adjudicate between alternative theoretical models of working memory on the basis of the effects of interference from articulatory suppression, irrelevant speech, and irrelevant nonspeech. In Experiment 1 we examined fMRI signal changes induced by each type of irrelevant information while subjects performed a probed recall task. Within a principally frontal and left-lateralized network of brain regions, articulatory suppression caused an increase in activity during item presentation, whereas both irrelevant speech and nonspeech caused relative activity reductions during the subsequent delay interval. In Experiment 2, the specific timing of interference was manipulated in a delayed serial recall task. Articulatory suppression was found to be most consequential when it coincided with item presentation, whereas both irrelevant speech and irrelevant nonspeech effects were strongest when limited to the subsequent delay period. Taken together, these experiments provide convergent evidence for a dissociation of articulatory suppression from the 2 irrelevant sound conditions. Implications of these findings are considered for 4 prominent theories of working memory.

In recent years, research applying functional neuroimaging to the study of cue-elicited drug craving has emerged. This research has begun to identify a distributed system of brain activity during drug craving. A review of this literature suggested that expectations regarding the opportunity to use a drug affected the pattern of neural responses elicited by drug cues. Using functional magnetic resonance imaging (fMRI), we examined the effects of smoking expectancy on the neural response to neutral (e.g., roll of tape) and smoking-related (a cigarette) stimuli in male cigarette smokers deprived of nicotine for 8 hr. As predicted, several brain regions (e.g., the anterior cingulate cortex) exhibited differential activation during cigarette versus neutral cue exposure. Moreover, we found that subregions of the prefrontal cortex (i.e., ventromedial, ventrolateral, and dorsolateral prefrontal cortices) showed cue-elicited activation that was modulated by smoking expectancy. These results highlight the importance of perceived drug use opportunity in the neurobiological response to drug cues.

Background: Functional disturbances in reward-related brain systems are thought to play a role in the development of mood, impulse, and substance-abuse disorders. Studies in nonhuman primates have identified brain regions, including the dorsal/ventral striatum and orbital-frontal cortex, in which neural activity is modulated by reward. Recent studies in adults have concurred with these findings by observing reward-contingent blood oxygen level-dependent (BOLD) responses in these regions during functional magnetic resonance imaging (fMRI) paradigms; however, no previous studies indicate whether comparable modulations of neural activity exist in the brain reward systems of children and adolescents., Methods: We used event-related fMRI and a behavioral paradigm modeled on previous work in adults to study brain responses to monetary gains and losses in psychiatrically healthy children and adolescents as part of a program examining the neural substrates of anxiety and depression in youth., Results: Regions and time-courses of reward-related activity were similar to those observed in adults with condition-dependent BOLD changes in the ventral striatum and lateral and medial orbital-frontal cortex; specifically, these regions showed larger responses to positive than to negative feedback., Conclusions: These results provide further evidence for the value of event-related fMRI in examining reward systems of the brain, demonstrate the feasibility of this approach in children and adolescents, and establish a baseline from which to understand the pathophysiology of reward-related psychiatric disorders in youth.

Unlabelled: Over the past two decades, there has been an explosion in the use of imaging technology to study the structure and function of the human brain. The purpose of this article is to explore how functional neuroimaging has been applied to the study of speech production. This article begins with a brief review of neuroimaging methods and limitations. Then, two approaches that can be used to study the brain areas that support speech production are illustrated. The first approach is based upon comparisons across different types of language production tasks; the second approach is based upon comparing the effects of different types of stimuli within a single task. Results obtained using these approaches will be used to dissociate the contributions of different brain regions involved in speech production. For example, evidence will be presented that Broca's area contributes to phonological encoding, whereas motor cortex, the supplementary motor area (SMA), and the cerebellum support phonetic encoding and articulation., Learning Outcomes: As a result of this activity, the participant will be able to describe basic methods for conducting a positron emission tomography study and a functional magnetic resonance imaging study. The participant will also be introduced to two approaches for fractionating the brain regions involved in speech production: (1) comparisons between tasks, and (2) manipulations of stimulus materials. Finally, the participant will be able to summarize a cognitive model of the components of speech production that will be introduced, and potential mappings between these components and particular brain regions will be discussed.

Neuropsychology and neuroimaging both provide information about the relationship between brain structure and function, and thus attempt to understand if the neural basis of cognition should benefit from converging results obtained across the two methods. However, serious attempts to integrate the two methodologies face several challenges, such as differences in basic paradigm designs. To illustrate these points, this article will review neuropsychological and neuroimaging research in the area of working memory. Points of discussion will include discrepancies between neuropsychological and neuroimaging evidence for domain-specific rehearsal systems, the role of left inferior parietal cortex in phonological storage, and the contributions of Brocas area and the cerebellum to articulatory rehearsal. Methodological factors and assumptions that may account for these discrepancies, and the steps that could be taken to overcome them, will be evaluated. The overall objective of this "case study" is to encourage neuroimagers and neuropsychologists to evaluate seriously the results obtained in both methodologies when formulating interpretations of their data and when designing new studies.

In the Italian language, spelling is consistently related to pronunciation, whereas English words that are spelled similarly are often pronounced differently. An imaging study now shows that native language affects the brain regions activated by reading aloud.

Functional neuroimaging was used to investigate three factors that affect reading performance: first, whether a stimulus is a word or pronounceable non-word (lexicality), second, how often a word is encountered (frequency), and third, whether the pronunciation has a predictable spelling-to-sound correspondence (consistency). Comparisons between word naming (reading) and visual fixation scans revealed stimulus-related activation differences in seven regions. A left frontal region showed effects of consistency and lexicality, indicating a role in orthographic to phonological transformation. Motor cortex showed an effect of consistency bilaterally, suggesting that motoric processes beyond high-level representations of word phonology influence reading performance. Implications for the integration of these results into theoretical models of word reading are discussed.

The effects of practice on the functional anatomy observed in two different tasks, a verbal and a motor task, are reviewed in this paper. In the first, people practiced a verbal production task, generating an appropriate verb in response to a visually presented noun. Both practiced and unpracticed conditions utilized common regions such as visual and motor cortex. However, there was a set of regions that was affected by practice. Practice produced a shift in activity from left frontal, anterior cingulate, and right cerebellar hemisphere to activity in Sylvian-insular cortex. Similar changes were also observed in the second task, a task in a very different domain, namely the tracing of a maze. Some areas were significantly more activated during initial unskilled performance (right premotor and parietal cortex and left cerebellar hemisphere); a different region (medial frontal cortex, "supplementary motor area") showed greater activity during skilled performance conditions. Activations were also found in regions that most likely control movement execution irrespective of skill level (e.g., primary motor cortex was related to velocity of movement). One way of interpreting these results is in a "scaffolding-storage" framework. For unskilled, effortful performance, a scaffolding set of regions is used to cope with novel task demands. Following practice, a different set of regions is used, possibly representing storage of particular associations or capabilities that allow for skilled performance. The specific regions used for scaffolding and storage appear to be task dependent.

This review discusses how neuroimaging can contribute to our understanding of a fundamental aspect of skilled reading: the ability to pronounce a visually presented word. One contribution of neuroimaging is that it provides a tool for localizing brain regions that are active during word reading. To assess the extent to which similar results are obtained across studies, a quantitative review of nine neuroimaging investigations of word reading was conducted. Across these studies, the results converge to reveal a set of areas active during word reading, including left-lateralized regions in occipital and occipitotemporal cortex, the left frontal operculum, bilateral regions within the cerebellum, primary motor cortex, and the superior and middle temporal cortex, and medial regions in the supplementary motor area and anterior cingulate. Beyond localization, the challenge is to use neuroimaging as a tool for understanding how reading is accomplished. Central to this challenge will be the integration of neuroimaging results with information from other methodologies. To illustrate this point, this review will highlight the importance of spelling-to-sound consistency in the transformation from orthographic (word form) to phonological (word sound) representations, and then explore results from three neuroimaging studies in which the spelling-to-sound consistency of the stimuli was deliberately varied. Emphasis is placed on the pattern of activation observed within the left frontal cortex, because the results provide an example of the issues and benefits involved in relating neuroimaging results to behavioral results in normal and brain damaged subjects, and to theoretical models of reading.

Practice of a novel task leads to improved performance. The brain mechanisms associated with practice-induced improvement in performance are largely unknown. To address this question we have examined the functional anatomy of the human brain with positron emission tomography (PET) during the naive and practiced performance of a simple verbal response selection task (saying an appropriate verb for a visually presented noun). As a control state, subjects were asked to repeat the visually presented nouns. Areas of the brain most active during naive performance (anterior cingulate, left prefrontal and left posterior temporal cortices, and the right cerebellar hemisphere), compared to repeating the visually presented nouns, were all significantly less active during practiced performance. These changes were accompanied by changes in the opposite direction in sylvian-insular cortex bilaterally and left medial extrastriate cortex. In effect, brief practice made the cortical circuitry used for verbal response selection indistinguishable from simple word repetition. Introduction of a novel list of words reversed the learning-related effects. These results indicate that two distinct circuits can be used for verbal response selection and normal subjects can change the brain circuits used during task performance following less than 15 min of practice. One critical factor in determining the circuitry used appears to be the degree to which a task is learned or automatic.