Two systems of resting state connectivity between the insula and cingulate cortex

The insula and cingulate cortices are implicated in emotional, homeostatic/allostatic, sensorimotor, and cognitive functions. Non‐human primates have specific anatomical connections between sub‐divisions of the insula and cingulate. Specifically, the anterior insula projects to the pregenual anterior cingulate cortex (pACC) and the anterior and posterior mid‐cingulate cortex (aMCC and pMCC); the mid‐posterior insula only projects to the posterior MCC (pMCC). In humans, functional neuroimaging studies implicate the anterior insula and pre/subgenual ACC in emotional processes, the mid‐posterior insula with awareness and interoception, and the MCC with environmental monitoring, response selection, and skeletomotor body orientation. Here, we tested the hypothesis that distinct resting state functional connectivity could be identified between (1) the anterior insula and pACC/aMCC; and (2) the entire insula (anterior, middle, and posterior insula) and the pMCC. Functional connectivity was assessed from resting state fMRI scans in 19 healthy volunteers using seed regions of interest in the anterior, middle, and posterior insula. Highly correlated, low‐frequency oscillations (< 0.05 Hz) were identified between specific insula and cingulate subdivisions. The anterior insula was shown to be functionally connected with the pACC/aMCC and the pMCC, while the mid/posterior insula was only connected with the pMCC. These data provide evidence for a resting state anterior insula–pACC/aMCC cingulate system that may integrate interoceptive information with emotional salience to form a subjective representation of the body; and another system that includes the entire insula and MCC, likely involved in environmental monitoring, response selection, and skeletomotor body orientation. Human Brain Mapp 2009. © 2008 Wiley‐Liss, Inc.     

Relationships between years of education,regional grey matter volumes,and working memory-related brain activity in healthy older adults

The aim of this study was to examine the relationships between educational attainment, regional grey matter volume, and functional working memory-related brain activation in older adults. The final sample included 32 healthy older adults with 8 to 22 years of education. Structural magnetic resonance imaging (MRI) was used to measure regional volume and functional MRI was used to measure activation associated with performing an n-back task. A positive correlation was found between years of education and cortical grey matter volume in the right medial and middle frontal gyri, in the middle and posterior cingulate gyri, and in the right inferior parietal lobule. The education by age interaction was significant for cortical grey matter volume in the left middle frontal gyrus and in the right medial cingulate gyrus. In this region, the volume loss related to age was larger in the low than high-education group. The education by age interaction was also significant for task-related activity in the left superior, middle and medial frontal gyri due to the fact that activation increased with age in those with higher education. No correlation was found between regions that are structurally related with education and those that are functionally related with education and age. The data suggest a protective effect of education on cortical volume. Furthermore, the brain regions involved in the working memory network are getting more activated with age in those with higher educational attainment.     

Activation likelihood estimation meta‐analysis of brain correlates of placebo analgesia in human experimental pain

Placebo analgesia (PA) is one of the most studied placebo effects. Brain imaging studies published over the last decade, using either positron emission tomography (PET) or functional magnetic resonance imaging (fMRI), suggest that multiple brain regions may play a pivotal role in this process. However, there continues to be much debate as to which areas consistently contribute to placebo analgesia‐related networks. In the present study, we used activation likelihood estimation (ALE) meta‐analysis, a state‐of‐the‐art approach, to search for the cortical areas involved in PA in human experimental pain models. Nine fMRI studies and two PET studies investigating cerebral hemodynamic changes were included in the analysis. During expectation of analgesia, activated foci were found in the left anterior cingulate, right precentral, and lateral prefrontal cortex and in the left periaqueductal gray (PAG). During noxious stimulation, placebo‐related activations were detected in the anterior cingulate and medial and lateral prefrontal cortices, in the left inferior parietal lobule and postcentral gyrus, anterior insula, thalamus, hypothalamus, PAG, and pons; deactivations were found in the left mid‐ and posterior cingulate cortex, superior temporal and precentral gyri, in the left anterior and right posterior insula, in the claustrum and putamen, and in the right thalamus and caudate body. Our results suggest on one hand that the modulatory cortical networks involved in PA largely overlap those involved in the regulation of emotional processes, on the other that brain nociceptive networks are downregulated in parallel with behavioral analgesia. Hum Brain Mapp, 2013. © 2011 Wiley Periodicals, Inc.     

Altered brain activation during response inhibition in children with primary nocturnal enuresis: An fMRI study

Nocturnal enuresis is a common developmental disorder in children, and primary nocturnal enuresis (PNE) is the dominant subtype. The main purpose of this study was to investigate brain functional abnormalities specifically related to motor response inhibition in children with PNE using fMRI in combination with a Go/NoGo task. Twenty‐two children with PNE and 22 healthy children, group‐matched for age and sex, took part in this experiment. Although no significant between‐group differences in task performance accuracy were observed, PNE patients showed significantly longer response times on average. There were several brain regions with reduced activation during motor response inhibition in children with PNE: the bilateral inferior frontal gyri, right superior and middle frontal gyri, right inferior parietal lobe, bilateral cingulate gyri and insula. Our data indicate that response inhibition in children with PNE is associated with a relative lack of or delay in the maturation of prefrontal cortex circuitry that is known to suppress inappropriate responses. This result might give clues to understanding the pathophysiology of PNE. Hum Brain Mapp, 2012. © 2011 Wiley Periodicals, Inc.     

Direct current stimulation over the human sensorimotor cortex modulates the brain's hemodynamic response to tactile stimulation

Tactile stimuli produce afferent signals that activate specific regions of the cerebral cortex. Noninvasive transcranial direct current stimulation (tDCS) effectively modulates cortical excitability. We therefore hypothesised that a single session of tDCS targeting the sensory cortices would alter the cortical response to tactile stimuli. This hypothesis was tested with a block‐design functional magnetic resonance imaging protocol designed to quantify the blood oxygen level‐dependent response to controlled sinusoidal pressure stimulation applied to the right foot sole, as compared with rest, in 16 healthy young adults. Following sham tDCS, right foot sole stimulation was associated with activation bilaterally within the precentral cortex, postcentral cortex, middle and superior frontal gyri, temporal lobe (subgyral) and cingulate gyrus. Activation was also observed in the left insula, middle temporal lobe, superior parietal lobule, supramarginal gyrus and thalamus, as well as the right inferior parietal lobule and claustrum (false discovery rate corrected, P < 0.05). To explore the regional effects of tDCS, brain regions related to somatosensory processing, and cortical areas underneath each tDCS electrode, were chosen as regions of interest. Real tDCS, as compared with sham tDCS, increased the percent signal change associated with foot stimulation relative to rest in the left posterior paracentral lobule. These results indicate that tDCS acutely modulated the cortical responsiveness to controlled foot pressure stimuli in healthy adults. Further study is warranted, in both healthy individuals and patients with sensory impairments, to link tDCS‐induced modulation of the cortical response to tactile stimuli with changes in somatosensory perception.     

Brain mechanisms for processing affective touch

Despite the crucial role of touch in social development, there is very little functional magnetic resonance imaging (fMRI) research on brain mechanisms underlying social touch processing. The “skin as a social organ” hypothesis is supported by the discovery of C‐tactile (CT) nerves that are present in hairy skin and project to the insular cortex. CT‐fibers respond specifically well to slow, gentle touch such as that which occurs during close social interactions. Given the social significance of such touch researchers have proposed that the CT‐system represents an evolutionarily conserved mechanism important for normative social development. However, it is currently unknown whether brain regions other than the insula are involved in processing CT‐targeted touch. In the current fMRI study, we sought to characterize the brain regions involved in the perception of CT‐supported affective touch. Twenty‐two healthy adults received manual brush strokes to either the arm or palm. A direct contrast of the blood‐oxygenation‐level‐dependent (BOLD) response to gentle brushing of the arm and palm revealed the involvement of a network of brain regions, in addition to the posterior insula, during CT‐targeted affective touch to the arm. This network included areas known to be involved in social perception and social cognition, including the right posterior superior temporal sulcus and the medial prefrontal cortex (mPFC)/dorso anterior cingulate cortex (dACC). Connectivity analyses with an mPFC/dACC seed revealed coactivation with the left insula and amygdala during arm touch. These findings characterize a network of brain regions beyond the insula involved in coding CT‐targeted affective touch. Hum Brain Mapp, 2013. © 2011 Wiley Periodicals, Inc.     

Children recruit distinct neural systems for implicit emotional face processing

The ability to properly distinguish facial emotions has a protracted development, not maturing until well into adolescence. Emotional faces activate emotion-specific neural networks in adults; whether these networks are operational in children is not known. Using an implicit face-processing task in 10-year-old children, we determined that the emotions of fear, disgust and sadness recruited distinct neural systems. These systems included a number of regions typically associated with processing emotions in adults, namely the amygdala and parahippocampal gyrus, insula and cingulate gyrus, as well as the fusiform and superior temporal gyri. Thus, in spite of immature behavioral responses to emotional faces in explicit tasks, neural networks for emotion-specific processing are present in young children.     

Localization of pain‐related brain activation: A meta‐analysis of neuroimaging data

A meta‐analysis of 140 neuroimaging studies was performed using the activation‐likelihood‐estimate (ALE) method to explore the location and extent of activation in the brain in response to noxious stimuli in healthy volunteers. The first analysis involved the creation of a likelihood map illustrating brain activation common across studies using noxious stimuli. The left thalamus, right anterior cingulate cortex (ACC), bilateral anterior insulae, and left dorsal posterior insula had the highest likelihood of being activated. The second analysis contrasted noxious cold with noxious heat stimulation and revealed higher likelihood of activation to noxious cold in the subgenual ACC and the amygdala. The third analysis assessed the implications of using either a warm stimulus or a resting baseline as the control condition to reveal activation attributed to noxious heat. Comparing noxious heat to warm stimulation led to peak ALE values that were restricted to cortical regions with known nociceptive input. The fourth analysis tested for a hemispheric dominance in pain processing and showed the importance of the right hemisphere, with the strongest ALE peaks and clusters found in the right insula and ACC. The fifth analysis compared noxious muscle with cutaneous stimuli and the former type was more likely to evoke activation in the posterior and anterior cingulate cortices, precuneus, dorsolateral prefrontal cortex, and cerebellum. In general, results indicate that some brain regions such as the thalamus, insula and ACC have a significant likelihood of activation regardless of the type of noxious stimuli, while other brain regions show a stimulus‐specific likelihood of being activated. Hum Brain Mapp, 2013. © 2011 Wiley Periodicals, Inc.     

Processing of nociceptive input from posterior to anterior insula in humans

Previous brain imaging studies have shown robust activations in the insula during nociceptive stimulation. Most activations involve the posterior insular cortex but they can cover all insular gyri in some fMRI studies. However, little is known about the timing of activations across the different insular sub‐regions. We report on the distribution of intracerebrally recorded nociceptive laser evoked potentials (LEPs) acquired from the full extent of the insula in 44 epileptic patients. Our study shows that both posterior and anterior subdivisions of the insular cortex respond to a nociceptive heat stimulus within a 200–400 ms latency range. This nociceptive cortical potential occurs firstly, and is larger, in the posterior granular insular cortex. The presence of phase reversals in LEP components in both posterior and anterior insular regions suggests activation of distinct, presumably functionally separate, sources in the posterior and anterior parts of the insula. Our results suggest that nociceptive input is first processed in the posterior insula, where it is known to be coded in terms of intensity and anatomical location, and then conveyed to the anterior insula, where the emotional reaction to pain is elaborated. Hum Brain Mapp 35:5486–5499, 2014. © 2014 Wiley Periodicals, Inc.     

Age-related differences in brain activity underlying identification of emotional expressions in faces

We used fMRI to explore brain activity in young and old adults,while they viewed and labeled faces expressing different emotionsas well as neutral expressions. Older adults had significantlygreater difficulty identifying expressions of sadness, angerand disgust than young adults. Both groups performed at ceilingfor happy expressions. The functional neuroimaging data revealedthat both young and old adults recruited a pattern of activitythat distinguished happy expressions from all other expressions,but the patterns were age-specific. Older adults showed increasedactivity in ventromedial prefrontal cortex, lingual gyrus andpremotor cortex for happy expressions, whereas younger adultsrecruited a more widely distributed set of regions includingthe amgydala, ventromedial prefrontal cortex, lateral prefrontalregions and bilateral inferior parietal and superior temporalareas. Conversely, younger adults showed more activity in thedorsal anterior cingulate for other types of expressions, andolder adults had more activity in dorsal cingulate, as wellas middle and inferior frontal gyri, somatosensory cortex, insulaand middle temporal regions. These results support previousresearch demonstrating age differences in brain activity duringemotional processing, and suggest possible age-related differencesin cognitive strategy during identification of happy faces,despite no effect of age on this ability.     

A longitudinal study of age‐ and gender‐related annual rate of volume changes in regional gray matter in healthy adults

The aim of this study was to analyze correlations among the annual rate of gray matter volume change, age, gender, and cerebrovascular risk factors in 381 healthy community‐dwelling subjects with a large age range by applying a longitudinal design over 6 years using brain magnetic resonance images (MRIs). Brain MRI data were processed with voxel‐based morphometry using a custom template by applying diffeomorphic anatomical registration using the exponentiated lie algebra procedure. The annual rate of regional gray matter volume change showed significant positive correlations with age in several regions, including the bilateral temporal pole, caudate nucleus, ventral and dorsolateral prefrontal cortices, insula, hippocampus, and temporoparietal cortex, whereas significant negative correlations with age were observed in several regions including the bilateral cingulate gyri and anterior lobe of the cerebellum. Additionally, a significant age‐by‐gender interaction was found for the annual rate of regional gray matter volume change in the bilateral hippocampus. No significant correlations were observed between the annual rate of regional gray matter volume change and body mass index or systolic blood pressure. A significant positive correlation between the annual rate of gray matter volume change and age indicates that the region shows not linear but accelerated gray matter loss with age. Therefore, evaluating the annual rate of the gray matter volume change with age in healthy subjects is important in understanding how gray matter volume changes with aging in each brain region and in anticipating what cognitive functions are likely to show accelerated decline with aging. Hum Brain Mapp 34:2292–2301, 2013. © 2012 Wiley Periodicals, Inc.     

Classification of delusions in Alzheimer's disease and their neural correlates

Background: Previous findings on neural correlates of delusion in Alzheimer's disease (AD) have been inconsistent because of methodological issues, such as treating multiple delusions as a single entity. In this retrospective study, we classified AD delusions and investigated their neural correlates by using single‐photon emission computed tomography data. Methods: We selected AD patients with delusions from our consecutive outpatients from 2004 to 2010. In this study, eight types of delusions were evaluated with Neuropsychiatric Inventory and classified by factor analysis. Twenty‐five of the patients also had single‐photon emission computed tomography data, which we used to assess the relationships between cerebral regions of hypoperfusion and hyperperfusion and each classified delusion. The relations were assessed using Statistical Parametric Mapping with normalization to the white matter cerebral blood flow. Results: The delusions were classified into three factors. Factor 1 consisted of a belief that his/her house is not his/her home, phantom boarder symptom, delusion of abandonment, and belief that one's spouse or others are not who they claim to be. Factor 1 was related to hypoperfusion in the right temporal pole and hyperperfusion in the medial frontal and precentral regions. Factor 2 consisted of delusion relating to the television and delusion of persecution. Factor 2 was related to hypoperfusion in the precuneus and hyperperfusion in the insula and thalamus. Factor 3 consisted of delusion of abandonment and delusional jealousy. Factor 3 was related to hypoperfusion in the right inferior temporal and frontal regions and hyperperfusion in the middle frontal gyrus, insula and posterior cingulate gyrus. Delusion of theft was not included in any factors, and it was related to hypoperfusion in the bilateral thalami and left posterior cingulate gyrus and hyperperfusion in the left inferior frontal regions and anterior cingulate gyrus. Conclusions: Delusions in AD were classifiable, and each classified delusion was related to different neural networks.     

The cingulum and cingulate U‐fibers in children and adolescents with autism spectrum disorders

The cingulum is the major fiber system connecting the cingulate and surrounding medial cortex and medial temporal lobe internally and with other brain areas. It is important for social and emotional functions related to core symptomatology in autism spectrum disorders (ASDs). While the cingulum has been examined in autism, the extensive system of cingulate U‐fibers has not been studied. Using probabilistic tractography, we investigated white matter fibers of the cingulate cortex by distinguishing its deep intra‐cingulate bundle (cingulum proper) and short rostral anterior, caudal anterior, posterior, and isthmus cingulate U‐fibers in 61 ASD and 54 typically developing children and adolescents. Increased mean and radial diffusivity of the left cingulum proper was observed in the ASD group, replicating previous findings on the cingulum. For cingulate U‐fibers, an atypical age‐related decline in right posterior cingulate U‐fiber volume was found in the ASD group, which appeared to be driven by an abnormally large volume in younger children. History of repetitive and restrictive behavior was negatively associated with right caudal anterior cingulate U‐fiber volume, linking cingulate motor areas with neighboring gyri. Aberrant development in U‐fiber volume of the right posterior cingulate gyrus may underlie functional abnormalities found in this region, such as in the default mode network.     

Differential functional brain network connectivity during visceral interoception as revealed by independent component analysis of fMRI time‐series

Influential theories of brain‐viscera interactions propose a central role for interoception in basic motivational and affective feeling states. Recent neuroimaging studies have underlined the insula, anterior cingulate, and ventral prefrontal cortices as the neural correlates of interoception. However, the relationships between these distributed brain regions remain unclear. In this study, we used spatial independent component analysis (ICA) and functional network connectivity (FNC) approaches to investigate time course correlations across the brain regions during visceral interoception. Functional magnetic resonance imaging (fMRI) was performed in thirteen healthy females who underwent viscerosensory stimulation of bladder as a representative internal organ at different prefill levels, i.e., no prefill, low prefill (100 ml saline), and high prefill (individually adapted to the sensations of persistent strong desire to void), and with different infusion temperatures, i.e., body warm (～37°C) or ice cold (4–8°C) saline solution. During Increased distention pressure on the viscera, the insula, striatum, anterior cingulate, ventromedial prefrontal cortex, amygdalo‐hippocampus, thalamus, brainstem, and cerebellar components showed increased activation. A second group of components encompassing the insula and anterior cingulate, dorsolateral prefrontal and posterior parietal cortices and temporal‐parietal junction showed increased activity with innocuous temperature stimulation of bladder mucosa. Significant differences in the FNC were found between the insula and amygdalo‐hippocampus, the insula and ventromedial prefrontal cortex, and the ventromedial prefrontal cortex and temporal‐parietal junction as the distention pressure on the viscera increased. These results provide new insight into the supraspinal processing of visceral interoception originating from an internal organ. Hum Brain Mapp 36:4438–4468, 2015. © 2015 Wiley Periodicals, Inc.     

A longitudinal functional magnetic resonance imaging study of language development in children 5 to 11 years old

OBJECTIVE: Language skills continue to develop rapidly in children during the school-age years, and the "snapshot" view of the neural substrates of language provided by current neuroimaging studies cannot capture the dynamic changes associated with brain development. The aim of this study was to conduct a 5-year longitudinal investigation of language development using functional magnetic resonance imaging in healthy children. METHODS: Thirty subjects enrolled at ages 5, 6, or 7 were examined annually for 5 years using a 3-Tesla magnetic resonance imaging scanner and a verb generation task. Data analysis was conducted based on a general linear model that was modified to investigate developmental changes whereas minimizing the potential for missing data. RESULTS: With increasing age, there is progressive participation in language processing by the inferior/middle frontal, middle temporal, and angular gyri of the left hemisphere and the lingual and inferior temporal gyri of the right hemisphere and regression of participation of the left posterior insula/extrastriate cortex, left superior frontal and right anterior cingulate gyri, and left thalamus. CONCLUSION: The age-related changes observed in this study provide evidence of increased neuroplasticity of language in this age group and may have implications for further investigations of normal and aberrant language development.     

fMRI and MEG analysis of visceral pain in healthy volunteers

Background Although many studies of painful rectal stimulation have found activation in the insula, cingulate, somatosensory, prefrontal cortices and thalamus, there is considerable variability when comparing functional magnetic resonance imaging (fMRI) results. Multiple factors may be responsible, including the model used in fMRI data analysis. Here, we assess the temporal response of activity to rectal barostat distension using novel fMRI and magnetoencephalography (MEG) analysis. Methods Liminal and painful rectal barostat balloon inflation thresholds were assessed in 14 female healthy volunteers. Subliminal, liminal and painful 40s periods of distension were applied in a pseudo‐randomized paradigm during fMRI and MEG neuroimaging. Functional MRI data analysis was performed comparing standard box‐car models of the full 40s of stimulus (Block) with models of the inflation (Ramp‐On) and deflation (Ramp‐Off) of the barostat. Similar models were used in MEG analysis of oscillatory activity. Key Results Modeling the data using a standard Block analysis failed to detect areas of interest found to be active using Ramp‐On and Ramp‐Off models. Ramp‐On generated activity in anterior insula and cingulate regions and other pain‐matrix associated areas. Ramp‐Off demonstrated activity of a network of posterior insula, SII and posterior cingulate. Active areas were consistent with those identified from MEG data. Conclusions & Inferences In studies of visceral pain, fMRI model design strongly influences the detected activity and must be accounted for to effectively explore the fMRI data in healthy subjects and within patient groups. In particular a strong cortical response is detected to inflation and deflation of the barostat, rather than to its absolute volume.     

Medial temporal lobe activity at recognition increases with the duration of mnemonic delay during an object working memory task

Object working memory (WM) engages a disseminated neural network, although the extent to which the length of time that data is held in WM influences regional activity within this network is unclear. We used functional magnetic resonance imaging to study a delayed matching to sample task in 14 healthy subjects, manipulating the duration of mnemonic delay. Across all lengths of delay, successful recognition was associated with the bilateral engagement of the inferior and middle frontal gyri and insula, the medial and inferior temporal, dorsal anterior cingulate and the posterior parietal cortices. As the length of time that data was held in WM increased, activation at recognition increased in the medial temporal, medial occipito-temporal, anterior cingulate and posterior parietal cortices. These results confirm the components of an object WM network required for successful recognition, and suggest that parts of this network, including the medial temporal cortex, are sensitive to the duration of mnemonic delay.     

Resting-state connectivity in the default mode network and insula during experimental low back pain简

Functional magnetic resonance imaging studies have shown that the insular cortex has a significant role in pain identification and information integration, while the default mode network is associated with cognitive and memory-related aspects of pain perception. However, changes in the functional connectivity between the default mode network and insula during pain remain unclear. This study used 3.0 T functional magnetic resonance imaging scans in 12 healthy subjects aged 24.8 ± 3.3 years to compare the differences in the functional activity and connectivity of the insula and default mode network between the baseline and pain condition induced by intramuscular injection of hypertonic saline. Compared with the baseline, the insula was more functionally connected with the medial prefrontal and lateral temporal cortices, whereas there was lower connectivity with the posterior cingulate cortex, precuneus and inferior parietal lobule in the pain condition. In addition, compared with baseline, the anterior cingulate cortex exhibited greater connectivity with the posterior insula, but lower connectivity with the anterior insula, during the pain condition. These data indicate that experimental low back pain led to dysfunction in the connectivity between the insula and default mode network resulting from an impairment of the regions of the brain related to cognition and emotion, suggesting the importance of the interaction between these regions in pain processing.     

Pooled analysis of brain activity in irritable bowel syndrome and controls during rectal balloon distension

Background Brain‐imaging literature of irritable bowel syndrome (IBS) suggests an abnormal brain–gut communication. We analyzed the literature to evaluate and compare the aspects of brain activity in individuals with IBS and control subjects experiencing controlled rectal stimulation. Methods PubMed was searched until September 2010. Data from 16 articles reporting brain activity during rectal balloon distensions in IBS compared to control groups was analyzed. Prevalence rates and pairwise activations were assessed using binomial distributions for 11 selected regions of interest. The data were aggregated to adjust for center effect. Key Results There was considerable variability in the literature regarding regions and their activity patterns in controls and individuals with IBS. There was no significant difference found in the thalamus, anterior cingulate cortex, posterior cingulate cortex, and prefrontal cortex, however, results show limited evidence of consensus for the anterior insula (AI) (P = 0.22). Pairwise activity results suggest that pairs involving the AI tend to have more consistent activity together than pairs which do not involve the AI (posterior insula and AI, P = 0.08; posterior cingulate cortex and AI, P = 0.16), however, no pairwise evaluation reached significance. Conclusions & Inferences Our pooled analysis demonstrates that the literature reports are quite heterogeneous but there is some evidence that there may be patterns of higher activity more common in individuals with IBS than in controls. A consensus, though, regarding study designs, analysis approach and reporting could create a clearer understanding of brain involvement in IBS pathophysiology.     

Brain activity during a motor learning task: an fMRI and skin conductance study

Measuring electrodermal activity (EDA) during fMRI is an effective means of studying the influence of task-related arousal, inferred from autonomic nervous system activity, on brain activation patterns. The goals of this study were: (1) to measure reliable EDA from healthy individuals during fMRI involving an effortful unilateral motor task, (2) to explore how EDA recordings can be used to augment fMRI data analysis. In addition to conventional hemodynamic modeling, skin conductance time series data were used as model waveforms to generate activation images from fMRI data. Activations from the EDA model produced significantly different brain regions from those obtained with a standard hemodynamic model, primarily in the insula and cingulate cortices. Onsets of the EDA changes were synchronous with the hemodynamic model, but EDA data showed additional transient features, such as a decrease in amplitude with time, and helped to provide behavioral evidence suggesting task difficulty decreased with movement repetition. Univariate statistics also confirmed that several brain regions showed early versus late session effects. Partial least squares (PLS) multivariate analysis of EDA and fMRI data provided complimentary, additional insight on how the motor network varied over the course of a single fMRI session. Brain regions identified in this manner included the insula, cingulate gyrus, pre- and postcentral gyri, putamen and parietal cortices. These results suggest that recording EDA during motor fMRI experiments provides complementary information that can be used to improve the fMRI analysis, particularly when behavioral or task effects are difficult to model a priori.