Inferior Frontal Sulcus Research Articles

Prefrontal thickening in PD with levodopa-induced dyskinesias: New evidence from cortical thickness measurement

PurposeNeurodegenerative processes in Parkinson's disease (PD) patients with levodopa-induced dyskinesias (LID) are still a matter of debate. Recently, we demonstrated that this clinical phenotype is associated with an abnormal gray matter increase in the prefrontal cortex when compared to PD without LID. This evidence was found by using voxel-based morphometry (VBM). However, VBM may not be the most appropriate procedure to assess cortical pathology, since its normalization/smoothing steps reduce the ability to anatomically characterize sulci and gyri. The aim of this study is to better delineate the LID-related anatomical abnormalities by using an advanced neuroimaging method that provides a direct and objective measure of the cortical morphology. MethodsSurface-based investigation of cortical mantle (cortical thickness) was carried out by using Freesurfer in two groups of treated PD patients with LID (no 29) and without LID (no 30), and one group of age- and sex-matched controls (no 24). ResultsCortical thickness analysis revealed a pronounced increase of thickness in the right inferior frontal sulcus in PD patients with LID with respect to PD patients without LID. DiscussionThe current study confirms our previous morphological findings on the role of the prefrontal cortex in the pathophysiology of LID and delineates with more precision the anatomical abnormalities characterizing this clinical phenotype.

Trait anxiety and the neural efficiency of manipulation in working memory

The present study investigates the effects of trait anxiety on the neural efficiency of working memory component functions (manipulation vs. maintenance) in the absence of threat-related stimuli. For the manipulation of affectively neutral verbal information held in working memory, high- and low-anxious individuals (N = 46) did not differ in their behavioral performance, yet trait anxiety was positively related to the neural effort expended on task processing, as measured by BOLD signal changes in fMRI. Higher levels of anxiety were associated with stronger activation in two regions implicated in the goal-directed control of attention—that is, right dorsolateral prefrontal cortex (DLPFC) and left inferior frontal sulcus—and with stronger deactivation in a region assigned to the brain’s default-mode network—that is, rostral–ventral anterior cingulate cortex. Furthermore, anxiety was associated with a stronger functional coupling of right DLPFC with ventrolateral prefrontal cortex. We interpret our findings as reflecting reduced processing efficiency in high-anxious individuals and point out the need to consider measures of functional integration in addition to measures of regional activation strength when investigating individual differences in neural efficiency. With respect to the functions of working memory, we conclude that anxiety specifically impairs the processing efficiency of (control-demanding) manipulation processes (as opposed to mere maintenance). Notably, this study contributes to an accumulating body of evidence showing that anxiety also affects cognitive processing in the absence of threat-related stimuli.Electronic supplementary materialThe online version of this article (doi:10.3758/s13415-012-0100-3) contains supplementary material, which is available to authorized users.

Sulcal morphology and volume of Broca’s area linked to handedness and sex

We investigated the effect of handedness and sex on: (i) sulcal contours defining PO and PTR and (ii) volume estimates of PO and PTR subfields in 40 left- and 42 right-handers. Results show an effect of handedness on discontinuity of the inferior frontal sulcus (IFS: P<0.01). Discontinuity of IFS was observed in: 43% left- and 62% right hemispheres in right-handers and in 65% left- and 48% right-hemispheres in left-handers. PO volume asymmetry was rightward in left-handed males (P=0.007) and females (P=0.02), showed a leftward trend in right-handed males (P=0.06), and was non-asymmetrical in right-handed females (P=0.96, i.e. left- and right-hemisphere PO volumes did not differ significantly). PO volume asymmetry in males differed significantly between handedness groups (P=0.001). Findings indicate a high degree of variability in the sulcal contours of PO and PTR and volume asymmetry of PO: the factors sex and handedness can explain some of this variability.

Poster #112 NO EVIDENCE THAT COMMON GENETIC RISK VARIANTS ARE SHARED BETWEEN SCHIZOPHRENIA AND AUTISM

Background: Although schizophrenic and control subjects differ on a variety of neuroanatomical measures, the specificity and sensitivity of any one measure for differentiating between groups are low. This study investigated the cumulative effect of deviant brain structure on diagnosis.Methods: Hemisphere and third ventricle volume and the normalized (Talairach) location of three association cortex sulcal landmarks were measured on high-resolution MRI scans in 37 male patients with schizophrenia and 33 male control subjects matched on age, handedness, and parental socioeconomic status.Results: While there were few group differences on individual anatomical measures, the 10 variables reliably discriminated between the two groups when used in concert in a discriminant function analysis (F[10,59] = 3.6, p < .0009) with 77% of the subjects correctly classified. Five of the measures (left posterior cingulate, left inferior frontal sulcus, right sylvian fissure, and left and right halves of the third ventricle) correlated significantly with the discriminant function (p < .005).Conclusions: This is the first study to demonstrate that schizophrenics can be distinguished from matched controls on the basis of brain anatomy alone. The risk of schizophrenia may depend on the total amount of neural deviance, rather than on anomalies in a single structure or circuit.

Absence of Face-specific Cortical Activity in the Complete Absence of Awareness: Converging Evidence from Functional Magnetic Resonance Imaging and Event-related Potentials

In this study, we explored the neural correlates of perceptual awareness during a masked face detection task. To assess awareness more precisely than in previous studies, participants employed a 4-point scale to rate subjective visibility. An event-related fMRI and a high-density ERP study were carried out. Imaging data showed that conscious face detection was linked to activation of fusiform and occipital face areas. Frontal and parietal regions, including the pre-SMA, inferior frontal sulcus, anterior insula/frontal operculum, and intraparietal sulcus, also responded strongly when faces were consciously perceived. In contrast, no brain area showed face-selective activity when participants reported no impression of a face. ERP results showed that conscious face detection was associated with enhanced N170 and also with the presence of a second negativity around 300 msec and a slow positivity around 415 msec. Again, face-related activity was absent when faces were not consciously perceived. We suggest that, under conditions of backward masking, ventral stream and fronto-parietal regions show similar, strong links of face-related activity to conscious perception and stress the importance of a detailed assessment of awareness to examine activity related to unseen stimulus events.

Does the inferior frontal sulcus play a functional role in deception? A neuronavigated theta-burst transcranial magnetic stimulation study

By definition, lying involves withholding the truth. Response inhibition may therefore be the cognitive function at the heart of deception. Neuroimaging research has shown that the same brain region that is activated during response inhibition tasks, namely the inferior frontal region, is also activated during deception paradigms. This led to the hypothesis that the inferior frontal region is the neural substrate critically involved in withholding the truth. In the present study, we critically examine the functional necessity of the inferior frontal region in withholding the truth during deception. We experimentally manipulated the neural activity level in right inferior frontal sulcus (IFS) by means of neuronavigated continuous theta-burst stimulation (cTBS). Individual structural magnetic resonance brain images (MRI) were used to allow precise stimulation in each participant. Twenty-six participants answered autobiographical questions truthfully or deceptively before and after sham and real cTBS. Deception was reliably associated with more errors, longer and more variable response times than truth telling. Despite the potential role of IFS in deception as suggested by neuroimaging data, the cTBS-induced disruption of right IFS did not affect response times or error rates, when compared to sham stimulation. The present findings do not support the hypothesis that the right IFS is critically involved in deception.

How Doctors Generate Diagnostic Hypotheses: A Study of Radiological Diagnosis with Functional Magnetic Resonance Imaging

BackgroundIn medical practice, diagnostic hypotheses are often made by physicians in the first moments of contact with patients; sometimes even before they report their symptoms. We propose that generation of diagnostic hypotheses in this context is the result of cognitive processes subserved by brain mechanisms that are similar to those involved in naming objects or concepts in everyday life.Methodology and Principal FindingsTo test this proposal we developed an experimental paradigm with functional magnetic resonance imaging (fMRI) using radiological diagnosis as a model. Twenty-five radiologists diagnosed lesions in chest X-ray images and named non-medical targets (animals) embedded in chest X-ray images while being scanned in a fMRI session. Images were presented for 1.5 seconds; response times (RTs) and the ensuing cortical activations were assessed. The mean response time for diagnosing lesions was 1.33 (SD ±0.14) seconds and 1.23 (SD ±0.13) seconds for naming animals. 72% of the radiologists reported cogitating differential diagnoses during trials (3.5 seconds). The overall pattern of cortical activations was remarkably similar for both types of targets. However, within the neural systems shared by both stimuli, activation was significantly greater in left inferior frontal sulcus and posterior cingulate cortex for lesions relative to animals.ConclusionsGeneration of diagnostic hypotheses and differential diagnoses made through the immediate visual recognition of clinical signs can be a fast and automatic process. The co-localization of significant brain activation for lesions and animals suggests that generating diagnostic hypotheses for lesions and naming animals are served by the same neuronal systems. Nevertheless, diagnosing lesions was cognitively more demanding and associated with more activation in higher order cortical areas. These results support the hypothesis that medical diagnoses based on prompt visual recognition of clinical signs and naming in everyday life are supported by similar brain systems.

Chronometry of word and picture identification: Common and modality-specific effects

Based on a previous fMRI connectivity analysis, we previously proposed that long-distance connections between left inferior frontal sulcus and left occipitotemporal sulcus mediate access to visual short-term memory both for written words and pictures enhancing conscious perception and successful encoding in an amodal manner. Using a 64-channel event-related potential electrode system in 19 young cognitively intact volunteers, we determined the chronometry of common and input-modality specific effects of word and picture identification and subsequent memory retrieval. Stimulus durations were calibrated per subject, modality and run so as to reach a 50% positive identification report. The earliest main effect of a positive identification report occurred between 180 and 200 ms, was common for both input-modalities, had a positive polarity and was located at around CPz. This effect was followed between 270 and 450 ms by additional common positive-polarity effects at centrofrontal electrode sites and by common negative effects at P7/P8, TP7/TP8 and T8. Each of the later effects was closely associated not only with identification but also with subsequent memory retrieval. The earliest input-modality specific effect of conscious identification that we detected occurred from 280 till 440 ms at P8. Our findings are in line with a model where the initial stages of perceptual identification and visual short-term memory access rely on long-distance connections that are shared between written words and pictures.

Functional organization of the left inferior precentral sulcus: Dissociating the inferior frontal eye field and the inferior frontal junction

Two eye fields have been described in the human lateral frontal cortex: the frontal eye field (FEF) and the inferior frontal eye field (iFEF). The FEF has been extensively studied and has been found to lie at the ventral part of the superior precentral sulcus. Much less research, however, has focused on the iFEF. Recently, it was suggested that the iFEF is located at the dorsal part of the inferior precentral sulcus. A similar location was proposed for the inferior frontal junction area (IFJ), an area thought to be involved in cognitive control processes. The present study used fMRI to clarify the topographical and functional relationship of the iFEF and the IFJ in the left hemispheres of individual participants. The results show that both the iFEF and the IFJ are indeed located at the dorsal part of the inferior precentral sulcus. Nevertheless, the activations were spatially dissociable in every individual examined. The IFJ was located more towards the depth of the inferior precentral sulcus, close to the junction with the inferior frontal sulcus, whereas the iFEF assumed a more lateral, posterior and superior position. Furthermore, the results provided evidence for a functional double dissociation: the iFEF was activated only in a comparison of saccades vs. button presses, but not in a comparison of incongruent vs. congruent Stroop conditions, while the opposite pattern was found at the IFJ. These results provide evidence for a spatial and functional dissociation of two directly adjacent areas in the left posterior frontal lobe.

Neural correlates of evidence accumulation in a perceptual decision task

Sequential sampling models provide a useful framework for understanding human decision making. A key component of these models is an evidence accumulation process in which information is accrued over time to a threshold, at which point a choice is made. Previous neurophysiological studies on perceptual decision making have suggested accumulation occurs only in sensorimotor areas involved in making the action for the choice. Here we investigated the neural correlates of evidence accumulation in the human brain using functional magnetic resonance imaging (fMRI) while manipulating the quality of sensory evidence, the response modality, and the foreknowledge of the response modality. We trained subjects to perform a random dot motion direction discrimination task by either moving their eyes or pressing buttons to make their responses. In addition, they were cued about the response modality either in advance of the stimulus or after a delay. We isolated fMRI responses for perceptual decisions in both independently defined sensorimotor areas and task-defined nonsensorimotor areas. We found neural signatures of evidence accumulation, a higher fMRI response on low coherence trials than high coherence trials, primarily in saccade-related sensorimotor areas (frontal eye field and intraparietal sulcus) and nonsensorimotor areas in anterior insula and inferior frontal sulcus. Critically, such neural signatures did not depend on response modality or foreknowledge. These results help establish human brain areas involved in evidence accumulation and suggest that the neural mechanism for evidence accumulation is not specific to effectors. Instead, the neural system might accumulate evidence for particular stimulus features relevant to a perceptual task.

Speech Facilitation by Left Inferior Frontal Cortex Stimulation

SummaryElectrophysiological studies in humans and animals suggest that noninvasive neurostimulation methods such as transcranial direct current stimulation (tDCS) can elicit long-lasting [1], polarity-dependent [2] changes in neocortical excitability. Application of tDCS can have significant and selective behavioral consequences that are associated with the cortical location of the stimulation electrodes and the task engaged during stimulation [3–8]. However, the mechanism by which tDCS affects human behavior is unclear. Recently, functional magnetic resonance imaging (fMRI) has been used to determine the spatial topography of tDCS effects [9–13], but no behavioral data were collected during stimulation. The present study is unique in this regard, in that both neural and behavioral responses were recorded using a novel combination of left frontal anodal tDCS during an overt picture-naming fMRI study. We found that tDCS had significant behavioral and regionally specific neural facilitation effects. Furthermore, faster naming responses correlated with decreased blood oxygen level-dependent (BOLD) signal in Broca's area. Our data support the importance of Broca's area within the normal naming network and as such indicate that Broca's area may be a suitable candidate site for tDCS in neurorehabilitation of anomic patients, whose brain damage spares this region.

Brain activation during audiovisual exposure anticipates future perception of ambiguous speech

In modern perceptual neuroscience, the focus of interest has shifted from a restriction to individual modalities to an acknowledgement of the importance of multisensory processing. One particularly well-known example of cross-modal interaction is the McGurk illusion. It has been shown that this illusion can be modified, such that it creates an auditory perceptual bias that lasts beyond the duration of audiovisual stimulation, a process referred to as cross-modal recalibration (Bertelson et al., 2003). Recently, we have suggested that this perceptual bias is stored in auditory cortex, by demonstrating the feasibility of retrieving the subjective perceptual interpretation of recalibrated ambiguous phonemes from functional magnetic resonance imaging (fMRI) measurements in these regions (Kilian-Hütten et al., 2011). However, this does not explain which brain areas integrate the information from the two senses and represent the origin of the auditory perceptual bias. Here we analyzed fMRI data from audiovisual recalibration blocks, utilizing behavioral data from perceptual classifications of ambiguous auditory phonemes that followed these blocks later in time. Adhering to this logic, we could identify a network of brain areas (bilateral inferior parietal lobe [IPL], inferior frontal sulcus [IFS], and posterior middle temporal gyrus [MTG]), whose activation during audiovisual exposure anticipated auditory perceptual tendencies later in time. We propose a model in which a higher-order network, including IPL and IFS, accommodates audiovisual integrative learning processes, which are responsible for the installation of a perceptual bias in auditory regions. This bias then determines constructive perceptual processing.

Simple autonomic seizures and ictal enuresis

Human micturition is physiologically controlled via a complex and finely tuned network of cortical and subcortical regions, hitherto not fully understood. We report the case of a 42-year-old man with juvenile myoclonic epilepsy (JME) and post-traumatic epilepsy. Ictal enuresis was the only manifestation of the de novo post-traumatic simple autonomic seizures. Source analysis of the ictal epileptiform discharges showed activation of the cortical areas surrounding the right inferior frontal sulcus, adjacent to the lesional zone. The case depicted here further endorses recent neuroimaging studies which strongly implicate this cortical region in the regulation and the initiation of the micturition.

What difference does a year of schooling make?

Early elementary schooling in 2nd and 3rd grades (ages 7-9) is an important period for the acquisition and mastery of basic mathematical skills. Yet, we know very little about neurodevelopmental changes that might occur over a year of schooling. Here we examine behavioral and neurodevelopmental changes underlying arithmetic problem solving in a well-matched group of 2nd (n = 45) and 3rd (n = 45) grade children. Although 2nd and 3rd graders did not differ on IQ or grade- and age-normed measures of math, reading and working memory, 3rd graders had higher raw math scores (effect sizes = 1.46-1.49) and were more accurate than 2nd graders in an fMRI task involving verification of simple and complex two-operand addition problems (effect size = 0.43). In both 2nd and 3rd graders, arithmetic complexity was associated with increased responses in right inferior frontal sulcus and anterior insula, regions implicated in domain-general cognitive control, and in left intraparietal sulcus (IPS) and superior parietal lobule (SPL) regions important for numerical and arithmetic processing. Compared to 2nd graders, 3rd graders showed greater activity in dorsal stream parietal areas right SPL, IPS and angular gyrus (AG) as well as ventral visual stream areas bilateral lingual gyrus (LG), right lateral occipital cortex (LOC) and right parahippocampal gyrus (PHG). Significant differences were also observed in the prefrontal cortex (PFC), with 3rd graders showing greater activation in left dorsal lateral PFC (dlPFC) and greater deactivation in the ventral medial PFC (vmPFC). Third graders also showed greater functional connectivity between the left dlPFC and multiple posterior brain areas, with larger differences in dorsal stream parietal areas SPL and AG, compared to ventral stream visual areas LG, LOC and PHG. No such between-grade differences were observed in functional connectivity between the vmPFC and posterior brain regions. These results suggest that even the narrow one-year interval spanning grades 2 and 3 is characterized by significant arithmetic task-related changes in brain response and connectivity, and argue that pooling data across wide age ranges and grades can miss important neurodevelopmental changes. Our findings have important implications for understanding brain mechanisms mediating early maturation of mathematical skills and, more generally, for educational neuroscience.

Neocortical thinning in “benign” mesial temporal lobe epilepsy

In refractory mesial temporal lobe epilepsy (MTLE) extrahippocampal and neocortical abnormalities have been described in patients with or without mesial temporal sclerosis (MTS). Recently we observed gray matter reductions in regions outside the hippocampus in benign MTLE with or without MTS. Cortical thickness has been proposed as a viable methodologic alternative for assessment of neuropathologic changes in extratemporal regions. Herein, we aimed to use this technique to describe cortical abnormalities in patients with benign TLE. Whole-brain cortical thickness analysis (FreeSurfer) was performed in 32 unrelated patients with benign TLE [16 patients with signs of MTS on magnetic resonance imaging (MRI), pMTLE; 16 without, nMTLE] and 44 healthy controls. In the pMTLE group, the most significant thinning was found in the sensorimotor cortex bilaterally but was more extensive in the left hemisphere (false discovery rate, p < 0.05). Other areas were localized in the occipital cortex, left supramarginal gyrus, left superior parietal gyrus, left paracentral sulcus, left inferior/middle/superior frontal gyrus, left inferior frontal sulcus, right cingulate cortex, right superior frontal gyrus, right inferior parietal gyrus, right fusiform gyrus, and cuneus/precuneus. In the nMTLE, a similar neurodegenerative pattern was detected, although not surviving correction for multiple comparisons. Direct comparison between pMTLE and nMTLE did not reveal significant changes. Patients with either benign pMTLE or nMTLE showed comparable cortical thinning, mainly confined to the sensorimotor cortex. This finding that is not appreciated on routine MRI supports the hypothesis that similar to refractory MTLE, even in benign MTLE, pathology in neocortical regions maybe implicated in the pathophysiology of this syndrome.

Technology, expertise and social cognition in human evolution

Paleolithic stone tools provide concrete evidence of major developments in human behavioural and cognitive evolution. Of particular interest are evolving cognitive mechanisms implied by the cultural transmission of increasingly complex prehistoric technologies, hypothetically including motor resonance, causal reasoning and mentalizing. To test the relevance of these mechanisms to specific Paleolithic technologies, we conducted a functional magnetic resonance imaging study of Naïve, Trained and Expert subjects observing two toolmaking methods of differing complexity and antiquity: the simple 'Oldowan' method documented by the earliest tools 2.5 million years ago; and the more complex 'Acheulean' method used to produce refined tools 0.5 million years ago. Subjects observed 20-s video clips of an expert demonstrator, followed by behavioural tasks designed to maintain attention. Results show that observational understanding of Acheulean toolmaking involves increased demands for the recognition of abstract technological intentions. Across subject groups, Acheulean compared with Oldowan toolmaking was associated with activation of left anterior intraparietal and inferior frontal sulci, indicating the relevance of resonance mechanisms. Between groups, Naïve subjects relied on bottom-up kinematic simulation in the premotor cortex to reconstruct unfamiliar intentions, and Experts employed a combination of familiarity-based sensorimotor matching in the posterior parietal cortex and top-down mentalizing involving the medial prefrontal cortex. While no specific differences between toolmaking technologies were found for Trained subjects, both produced frontal activation relative to Control, suggesting focused engagement with toolmaking stimuli. These findings support motor resonance hypotheses for the evolutionary origins of human social cognition and cumulative culture, directly linking these hypotheses with archaeologically observable behaviours in prehistory.

Anatomy of Language Impairments in Primary Progressive Aphasia

Primary progressive aphasia (PPA) is a clinical dementia syndrome characterized by progressive decline in language function but relative sparing of other cognitive domains. There are three recognized PPA variants: agrammatic, semantic, and logopenic. Although each PPA subtype is characterized by the nature of the principal deficit, individual patients frequently display subtle impairments in additional language domains. The present study investigated the distribution of atrophy related to performance in specific language domains (i.e., grammatical processing, semantic processing, fluency, and sentence repetition) across PPA variants to better understand the anatomical substrates of language. Results showed regionally specific relationships, primarily in the left hemisphere, between atrophy and impairments in language performance. Most notable was the neuroanatomical distinction between fluency and grammatical processing. Poor fluency was associated with regions dorsal to the traditional boundaries of Broca's area in the inferior frontal sulcus and the posterior middle frontal gyrus, whereas grammatical processing was associated with more widespread atrophy, including the inferior frontal gyrus and supramarginal gyrus. Repetition performance was correlated with atrophy in the posterior superior temporal gyrus. The correlation of atrophy with semantic processing impairment was localized to the anterior temporal poles. Atrophy patterns were more closely correlated with domain-specific performance than with subtype. These results show that PPA reflects a selective disruption of the language network as a whole, with no rigid boundaries between subtypes. Further, these atrophy patterns reveal anatomical correlates of language that could not have been surmised in patients with aphasia resulting from cerebrovascular lesions.

The relationship between the presence of sulcal pits and intelligence in human brains

Sulcal pits are hypothesized to form early during development and be under tighter genetic control than other regions of the cortex. We investigated the relationship between the presence of sulcal pits and intellectual ability, estimated with the full-scale, verbal, and performance intelligence quotient (IQ), in the brains of 78 healthy young adults. We automatically extracted sulcal pits from magnetic resonance images and developed a method for their automatic labeling. The difference in the number of sulcal pits between high and average IQ groups for each labeled region was statistically analyzed. We found that in the high verbal IQ group a sulcal pit was more frequently present in the left posterior inferior frontal sulcus (70% in the high IQ group vs. 40% in the average IQ group) and the right posterior inferior temporal sulcus (70% vs. 43%), which have been reported to be regions of language function. Greater mean curvature of the deep sulcal areas in these regions was shown for the high verbal IQ group. This provides the complementary morphological information about the presence of more sulcal pits. These findings suggest that factors influencing verbal intelligence may emerge in the language areas early during cortical development and may be under tight genetic control.

Faces and Eyes in Human Lateral Prefrontal Cortex

Much of the work on face-selective neural activity has focused on posterior, ventral areas of the human and non-human primate brain. However, electrophysiological and fMRI studies have identified face responses in the prefrontal cortex. Here we used fMRI to characterize these responses in the human prefrontal cortex compared with face selectivity in posterior ventral region. We examined a region at the junction of the right inferior frontal sulcus and the precentral sulcus (right inferior frontal junction or rIFJ) that responds more to faces than to several other object categories. We find that the rIFJ and the right fusiform face area (rFFA) are broadly similar in their responses to whole faces, headless bodies, tools, and scenes. Strikingly, however, while the rFFA preferentially responds to the whole face, the rIFJ response to faces appears to be driven primarily by the eyes. This dissociation provides clues to the functional role of the rIFJ face response. We speculate on this role with reference to emotion perception, gaze perception, and to behavioral relevance more generally.

Assembly and Use of New Task Rules in Fronto-parietal Cortex

Severe capacity limits, closely associated with fluid intelligence, arise in learning and use of new task rules. We used fMRI to investigate these limits in a series of multirule tasks involving different stimuli, rules, and response keys. Data were analyzed both during presentation of instructions and during later task execution. Between tasks, we manipulated the number of rules specified in task instructions, and within tasks, we manipulated the number of rules operative in each trial block. Replicating previous results, rule failures were strongly predicted by fluid intelligence and increased with the number of operative rules. In fMRI data, analyses of the instruction period showed that the bilateral inferior frontal sulcus, intraparietal sulcus, and presupplementary motor area were phasically active with presentation of each new rule. In a broader range of frontal and parietal regions, baseline activity gradually increased as successive rules were instructed. During task performance, we observed contrasting fronto-parietal patterns of sustained (block-related) and transient (trial-related) activity. Block, but not trial, activity showed effects of task complexity. We suggest that, as a new task is learned, a fronto-parietal representation of relevant rules and facts is assembled for future control of behavior. Capacity limits in learning and executing new rules, and their association with fluid intelligence, may be mediated by this load-sensitive fronto-parietal network.