Dorsal Anterior Insula Research Articles

Increased ventral striatal functional connectivity in patients with schizophrenia during reward anticipation

BackgroundGrowing evidence points towards dysfunction of the ventral striatum as a neural substrate of motivational impairments in schizophrenia. Ventral striatal activity during reward anticipation is generally reduced in patients with schizophrenia and specifically correlates with apathy. However, little is known about the cortico-striatal functional connectivity in patients with schizophrenia during reward anticipation and its relation to negative symptoms. ObjectivesThe aim of this study was to identify categorical group differences in ventral striatal functional connectivity during reward anticipation between patients with schizophrenia and healthy controls, and dimensional associations between cortico-striatal functional connectivity and negative symptom severity. MethodA total of 40 patients with schizophrenia (10 females) and 33 healthy controls (8 females) were included from two previously published studies. All participants performed a variant of the Monetary Incentive Delay Task while undergoing event-related fMRI. Functional connectivity was assessed using psychophysical interactions (PPI) with the left and right ventral striatum as seeds and the contrast [High Reward Anticipation – No Reward Anticipation]. Negative symptoms were assessed using the Brief Negative Symptom Scale. ResultsCompared to controls, patients with schizophrenia showed increased functional connectivity between the left ventral striatum and the left precuneus and right parahippocampal gyrus, two hubs of the default mode network (cluster-level threshold: FWE, p < .05). In addition, we found a negative association between apathy scores on the BNSS and increased functional connectivity between the left ventral striatum and the left ventral anterior insula / putamen and the left inferior frontal gyrus / dorsal anterior insula (cluster-level threshold: FWE, p < .05). ConclusionsOur results indicate that the patterns of increased functional connectivity between the ventral striatum and the dorsal default mode network during reward anticipation could act as a compensatory mechanism to regulate the activity of the ventral striatum. Our results also showed that functional connectivity patterns from the ventral striatum, much like its local activity, is specifically related to apathy, and not diminished expression.

Brain activity during pursuit and goal-conflict threat avoidance in major depressive disorder.

Threat avoidance is a prominent symptom of affective disorders, yet its biological basis remains poorly understood. Here, we used a validated task, the Joystick Operated Runway Task (JORT), combined with fMRI, to explore whether abnormal function in neural circuits responsible for avoidance underlies these symptoms. Eighteen individuals with major depressive disorder (MDD) and 17 unaffected controls underwent the task, which involved using physical effort to avoid threatening stimuli, paired with mild electric shocks on certain trials. Activity during anticipation and avoidance of threats was explored and compared between groups. Anticipation of aversive stimuli was associated with significant activation in the dorsal anterior cingulate cortex, superior frontal gyrus, and striatum, while active avoidance of aversive stimuli was associated with activity in dorsal anterior cingulate cortex, insula, and prefrontal cortex. There were no significant group differences in neural activity or behavioral performance on the JORT; however, participants with depression reported more dread while being chased on the task. The JORT effectively identified neural systems involved in avoidance and anticipation of aversive stimuli. However, the absence of significant differences in behavioral performance and activation between depressed and non-depressed groups suggests that MDD is not associated with abnormal function in these networks. Future research should investigate the basis of passive avoidance in major depression. Further, the JORT should be explored in patients with anxiety disorders, where threat avoidance may be a more prominent characteristic of the disorder.

Structural covariance of amygdala subregions is associated with trait aggression and endogenous testosterone in healthy individuals

Many studies point toward volume reductions in the amygdala as a potential neurostructural marker for trait aggression. However, most of these findings stem from clinical samples, rendering unclear whether the findings generalize to non-clinical populations. Furthermore, the notion of neural networks suggests that interregional correlations in gray matter volume (i.e., structural covariance) can explain individual differences in aggressive behavior beyond local univariate associations. Here, we tested whether structural covariance between amygdala subregions and the rest of the brain is associated with self-reported aggression in a large sample of healthy young students (n = 263; 49% women). Salivary testosterone concentrations were measured for a subset of n = 40 male and n = 36 female subjects, allowing us to investigate the influence of endogenous testosterone on structural covariance. Aggressive individuals showed enhanced covariance between left superficial amygdala (SFA) and left dorsal anterior insula (dAI), but lower covariance between right laterobasal amygdala (LBA) and right dorsolateral prefrontal cortex (dlPFC). These structural patterns overlap with functional networks involved in the genesis and regulation of aggressive behavior, respectively. With increasing endogenous testosterone, we observed stronger structural covariance between right centromedial amygdala (CMA) and right medial prefrontal cortex in men and between left CMA and bilateral orbitofrontal cortex in women. These results speak for structural covariance of amygdala subregions as a robust correlate of trait aggression in healthy individuals. Moreover, regions that showed structural covariance with the amygdala modulated by either testosterone or aggression did not overlap, suggesting a complex role of testosterone in human social behavior beyond facilitating aggressiveness.

Increased functional connectivity between presupplementary motor area and inferior frontal gyrus associated with the ability of motor response inhibition in obsessive-compulsive disorder.

Recent evidence suggests that presupplementary motor area (pre‐SMA) and inferior frontal gyrus (IFG) play an important role in response inhibition. However, no study has investigated the relationship between these brain networks at resting‐state and response inhibition in obsessive–compulsive disorder (OCD). We performed resting‐state functional magnetic resonance imaging scans and then measured the response inhibition of 41 medication‐free OCD patients and 49 healthy control (HC) participants by using the stop‐signal task outside the scanner. We explored the differences between OCD and HC groups in the functional connectivity of pre‐SMA and IFG associated with the ability of motor response inhibition. OCD patients showed a longer stop‐signal reaction time (SSRT). Compared to HC, OCD patients exhibit different associations between the ability of motor response inhibition and the functional connectivity between pre‐SMA and IFG, inferior parietal lobule, dorsal anterior cingulate cortex, insula, and anterior prefrontal cortex. Additional analysis to investigate the functional connectivity difference from the seed ROIs to the whole brain voxels revealed that, compared to HC, OCD exhibited greater functional connectivity between pre‐SMA and IFG. Also, this functional connectivity was positively correlated with the SSRT score. These results provide additional insight into the characteristics of the resting‐state functional connectivity of the regions belonging to the cortico‐striato‐thalamo‐cortical circuit and the cingulo‐opercular salience network, underlying the impaired motor response inhibition of OCD. In particular, we emphasize the importance of altered functional connectivity between pre‐SMA and IFG for the pathophysiology of motor response inhibition in OCD.

Brain Structural Changes in Carpal Tunnel Syndrome Patients: From the Perspectives of Structural Connectivity and Structural Covariance Network.

Carpal tunnel syndrome (CTS) is a common peripheral entrapment neuropathy. However, CTS-related changes of brain structural covariance and structural covariance networks (SCNs) patterns have not been clearly studied. To explore CTS-related brain changes from perspectives of structural connectivity and SCNs. Brain structural magnetic resonance images were acquired from 27 CTS patients and 19 healthy controls (HCs). Structural covariance and SCNs were constructed based on gray matter volume. The global network properties including clustering coefficient (Cp), characteristic path length (Lp), small-worldness index, global efficiency (Eglob), and local efficiency (Eloc) and regional network properties including degree, betweenness centrality (BC), and Eloc of a given node were calculated with graph theoretical analysis. Compared with HCs, the strength of structural connectivity between the dorsal anterior insula and medial prefrontal thalamus decreased (P <.001) in CTS patients. There was no intergroup difference of area under the curve for Cp, Lp¸ Eglob, and Eloc (all P >.05). The real-world SCN of CTS patients showed a small-world topology ranging from 2% to 32%. CTS patients showed lower nodal degrees of the dorsal anterior insula and medial prefrontal thalamus, and higher Eloc of a given node and BC in the lateral occipital cortex (P <.001) and the dorsolateral middle temporal gyrus (P <.001) than HCs, respectively. CTS had a profound impact on brain structures from perspectives of structural connectivity and SCNs.

The neural correlates of grandmaternal caregiving.

In many societies, grandmothers are important caregivers, and grandmaternal investment is often associated with improved grandchild well-being. Here, we present, to our knowledge, the first study to examine grandmaternal brain function. We recruited 50 grandmothers with at least one biological grandchild between 3 and 12 years old. Brain function was measured with functional magnetic resonance imaging as grandmothers viewed pictures of their grandchild, an unknown child, the same-sex parent of the grandchild, and an unknown adult. Grandmothers also completed questionnaires to measure their degree of involvement with and attachment to their grandchild. After controlling for age and familiarity of stimuli, viewing grandchild pictures activated areas involved with emotional empathy (insula and secondary somatosensory cortex) and movement (motor cortex and supplementary motor area). Grandmothers who more strongly activated areas involved with cognitive empathy (temporo-parietal junction and dorsomedial prefrontal cortex) when viewing pictures of the grandchild desired greater involvement in caring for the grandchild. Finally, compared with results from an earlier study of fathers, grandmothers more strongly activated regions involved with emotional empathy (dorsal anterior cingulate cortex, insula and secondary somatosensory cortex), and motivation (nucleus accumbens, ventral pallidum and caudate nucleus). All in all, our findings suggest that emotional empathy may be a key component of grandmaternal responses to their grandchildren.

Epilepsy and Ecstatic Experiences: The Role of the Insula.

Ecstatic epilepsy is a rare form of focal epilepsy in which the aura (beginning of the seizures) consists of a blissful state of mental clarity/feeling of certainty. Such a state has also been described as a “religious” or mystical experience. While this form of epilepsy has long been recognized as a temporal lobe epilepsy, we have accumulated evidence converging toward the location of the symptomatogenic zone in the dorsal anterior insula during the 10 last years. The neurocognitive hypothesis for the genesis of a mental clarity is the suppression of the interoceptive prediction errors and of the unexpected surprise associated with any incoming internal or external signal, usually processed by the dorsal anterior insula. This mimics a perfect prediction of the world and induces a feeling of certainty. The ecstatic epilepsy is thus an amazing model for the role of anterior insula in uncertainty and surprise.

To learn or to gain: neural signatures of exploration in human decision-making.

Individuals not only take actions to obtain immediate rewards but also to gain more information to guide future choices. An ideal exploration-exploitation balance is crucial for maximizing reward over the long run. However, the neural signatures of exploration in humans remain unclear. Using quantitative meta-analyses of functional magnetic resonance imaging experiments on exploratory behaviors, we sought to identify the concordant activity pertaining to exploration over a range of experiments. The results revealed that exploration activates concordant brain activity associated with risk (e.g., dorsal medial prefrontal cortex and anterior insula), cognitive control (e.g., dorsolateral prefrontal cortex and inferior frontal gyrus), and motor processing (e.g., premotor cortex). These stereotaxic maps of exploration may indicate that exploration is highly linked to risk processing, but is also specifically associated with regions involved in executive control processes. Although this explanation should be treated as exploratory, these findings support theories positing an important role for the prefrontal-insular-motor cortical network in exploration.

Cerebral Blood Flow in the Salience Network of Individuals with Alcohol Use Disorder.

Magnetic resonance imaging (MRI) studies have identified structural and functional differences in salience network nodes of individuals with alcohol use disorders (AUDs) after chronic exposure to alcohol. However, no studies have investigated cerebral blood flow (CBF) in nontreatment-seeking (NTS) individuals with AUD. In this work, we sought to quantify putative CBF deficits in NTS individuals relative to social drinking (SD) controls and determine if CBF in the salience network is associated with AUD severity. Fifteen NTS (36.5 ± 11.2years old, 30.0 ± 22.7 drinks/week) and 22 SD (35.6 ± 11.9 years old, 9.1 ± 5.7 drinks/week) underwent pseudocontinuous arterial spin labeling MRI. Compared with social drinkers, NTS individuals had significantly lower CBF in the right and left dorsal anterior insula, and the left ventral anterior and posterior insula. The Alcohol Use Disorder Identification Test (AUDIT) score showed a significant negative relationship with CBF in the bilateral caudal anterior cingulate cortex. In addition, a significant negative correlation was present between number of standard drinks consumed per week and the left frontal opercular CBF. These results provide evidence that insular CBF is negatively associated with heavy drinking, and that severity of alcohol use is related to CBF deficits in key nodes of the salience network. Longitudinal data are needed to understand if disruptions of CBF in the insula and the salience network are a predisposition for or a consequence of chronic AUD.

Interactive Effects of HIV Infection and Cannabis Use on Insula Subregion Functional Connectivity.

Chronic inflammation in the central nervous system is one mechanism through which human immunodeficiency virus (HIV) may lead to progressive cognitive decline. Given cannabis's (CB's) anti-inflammatory properties, use prevalence among people living with HIV (PLWH), and evidence implicating the insula in both, we examined independent and interactive effects of HIV and CB on insular circuitry, cognition, and immune function. We assessed resting-state functional connectivity (rsFC) of three insula subregions among 106 participants across four groups (co-occurring: HIV+/CB+; HIV-only: HIV+/CB-; CB-only: HIV-/CB+; controls: HIV-/CB-). Participants completed a neurocognitive battery assessing functioning across multiple domains and self-reported somatic complaints. Blood samples quantified immune function (T-cell counts) and inflammation (tumor necrosis factor alpha [TNF-α]). We observed interactive HIV × CB effects on rsFC strength between two anterior insula (aI) subregions and sensorimotor cortices such that, CB appeared to normalize altered rsFC among non-using PLWH. Specifically, compared to controls, HIV-only and CB-only groups displayed decreased dorsal anterior insula (DI) - postcentral gyrus rsFC and increased ventral anterior insula (VI) - supplementary motor area rsFC, whereas the co-occurring group displayed DI and VI rsFC more akin to that of controls. Altered DI - postcentral rsFC correlated with decreased processing speed and somatic complaints, but did not significantly correlate with inflammation (TNF-α). These outcomes implicate insula - sensorimotor neurocircuitries in HIV and CB and are consistent with prior work suggesting that CB use may normalize insula functioning among PLWH.

Burst spinal cord stimulation can attenuate pain and its affective components in chronic pain patients with high psychological distress: results from the prospective, international TRIUMPH study

BACKGROUND CONTEXTPsychological characteristics such as catastrophizing and depression have been shown to negatively impact outcome prognosis after spinal interventions. PURPOSETo evaluate whether high psychological distress, defined as clinically elevated levels of catastrophizing and depression, is associated with poorer outcomes after spinal cord stimulation utilizing a passive recharge burst stimulation design. This proprietary waveform may uniquely attenuate the emotional aspects of chronic pain given its affects on the medial pain pathway projecting to the dorsal anterior cingulate cortex and anterior insula. STUDY DESIGN/SETTINGSData were extracted from the prospective, multi-center, single-arm, international TRIUMPH study. The purpose of TRIUMPH was to assess long-term (2 years) safety and effectiveness of spinal cord stimulation for chronic pain in the trunk and/or limbs using a passive recharge enabled burst spinal cord stimulation (B-SCS) system. PATIENT SAMPLETwo subsets of study patients were identified; those with (n=31) and those without (n=54) high psychological distress. OUTCOME MEASURESPsychological and functional outcomes as well as pain intensity and impact of pain on life were administered at baseline and all follow intervals. Additionally, patient satisfaction and patient global impression of change were assessed at all follow-up intervals. METHODSPsychological distress (PD) was defined as a baseline score of ≥ 30 on the Pain Catastrophizing Scale (PCS) and ≥ 10 on the Patient Health Questionnaire Depression scale (PHQ-9). Nondistressed (ND) patients had scores below these thresholds on both scales. All patients were implanted with a B-SCS system and completed data collection for the 24-month follow-up visit. This study was funded by Abbott. JMH is a consultant for Abbott and has received <$20,000 in lifetime consulting fees from Abbott. SMF is a consultant for Abbott and has received >$50,000 in lifetime consulting fees from Abbott. BB is an Abbott employee. RAC is a former Abbott employee. JJY is a consultant for Abbott and has received <$2,500 in lifetime consulting fees from Abbott. RESULTSOf the 128 participants with 24-month data, 31 (24%) and 54 (35%) met the criteria for PD and ND, respectively. Baseline measures indicated a more severe chronic pain profile and worse quality of life in the PD group. Two years after implant, 71% were no longer clinically catastrophizing and 58% were no longer clinically depressed. Notably, more than half of the PD patients on antidepressants discontinued or decreased their medication. Health-related quality of life was 82% higher in the PD group at 24 months, reaching levels similar to the ND group. Psychological distress did not impact outcomes after SCS therapy; composite multi-responder rates were similar in the 2 groups throughout the follow-up period. Patient reported pain relief (58% PD vs. 61% ND) was equivalent in each group. In both groups, 81% were satisfied or very satisfied with the pain relief provided. CONCLUSIONSOur results showed that B-SCS appears to be as effective in a chronic pain population with high psychological distress as in those without distress. This may be due to the unique mechanism of action with the stimulation design involving the emotional-affective medial pain pathway in the brain.

Task-related neural mechanisms of persecutory ideation in schizophrenia and community monozygotic twin-pairs.

Perceptions of spiteful behavior are common, distinct from rational fear, and may undergird persecutory ideation. To test this hypothesis and investigate neural mechanisms of persecutory ideation, we employed a novel economic social decision‐making task, the Minnesota Trust Game (MTG), during neuroimaging in patients with schizophrenia (n = 30) and community monozygotic (MZ) twins (n = 38; 19 pairs). We examined distinct forms of mistrust, task‐related brain activation and connectivity, and investigated relationships with persecutory ideation. We tested whether co‐twin discordance on these measurements was correlated to reflect a common source of underlying variance. Across samples persecutory ideation was associated with reduced trust only during the suspiciousness condition, which assessed spite sensitivity given partners had no monetary incentive to betray. Task‐based activation contrasts for specific forms of mistrust were limited and unrelated to persecutory ideation. However, task‐based connectivity contrasts revealed a dorsal cingulate anterior insula network sensitive to suspicious mistrust, a left frontal–parietal (lF‐P) network sensitive to rational mistrust, and a ventral medial/orbital prefrontal (vmPFC/OFC) network that was sensitive to the difference between these forms of mistrust (all p < .005). Higher persecutory ideation was predicted only by reduced connectivity between the vmPFC/OFC and lF‐P networks (p = .005), which was only observed when the intentions of the other player were relevant. Moreover, co‐twin differences in persecutory ideation predicted co‐twin differences in both spite sensitivity and in vmPFC/OFC–lF‐P connectivity. This work found that interconnectivity may be particularly important to the complex neurobiology underlying persecutory ideation, and that unique environmental variance causally linked persecutory ideation, decision‐making, and brain connectivity.

Relationships Between Early Maternal Warmth and Social Connection: A Randomized Clinical Trial With Naltrexone.

Early experiences of having received maternal warmth predict responses to opportunities to connect with others later in life. However, the understanding of neurochemical mechanisms by which such relationships emerge remains incomplete. Endogenous opioids, involved in social connection in both animals and humans, may contribute to this link. Therefore, the current study examined a) relationships between early maternal warmth and brain and self-report responses to novel social targets (i.e., outcomes that may promote social connection) and b) the effect of the opioid antagonist, naltrexone, on such relationships. Eighty-two adult participants completed a retrospective report of early maternal warmth. On a second visit, participants were randomized to 50 mg of oral naltrexone (n = 42) or placebo (n = 40), followed by a magnetic resonance imaging scan where functional brain activity in response to images of novel social targets (strangers) was assessed. Approximately 24 hours later, participants reported on their feelings of social connection since leaving the scanner. In the placebo condition, greater early maternal warmth was associated with less dorsal anterior cingulate cortex, anterior insula, ventral striatum, and amygdala activity in response to images of novel social targets (r values ≥ -0.360, p values ≤ .031), and greater feelings of social connection (r = 0.524, p < .001) outside of the laboratory. The same relationships, however, were not present in the naltrexone condition. Results highlight relationships between early maternal warmth and responses to the social world at large and suggest that opioids might contribute to social connection by supporting the buffering effects of warm early life experiences on social connection later in life.Trial Registration: Clinical Trials NCT02818036.

Altered Functional Connectivity of Insular Subregions in Type 2 Diabetes Mellitus.

Diabetes-related brain damage can lead to cognitive decline and increase the risk of depression, but the neuropathological mechanism of this phenomenon remains unclear. Different insular subregions have obvious functional heterogeneity, which is related to many aspects of type 2 diabetes mellitus (T2DM)-related brain damage. However, little is known about changes in functional connectivity (FC) in insular subregions in patients with T2DM. Therefore, we aimed to investigate FC between different insular subregions and clinical/cognitive variables in patients with T2DM. Fifty-seven patients with T2DM and 55 healthy controls (HCs) underwent a neuropsychological assessment and resting-state FC examination. We defined three insular subregions, including the bilateral dorsal anterior insula (dAI), bilateral ventral anterior insula (vAI), and bilateral posterior insula (PI). We examined differences in FC between insular subregions and the whole brain in patients with T2DM compared with HCs. A correlation analysis was performed to examine the relationship between FC and clinical/cognitive variables. Compared with HCs, patients with T2DM showed significantly decreased FC between the dAI and the right inferior frontal gyrus, right superior/middle temporal gyrus, right hippocampus, and right precentral gyrus. FC between the vAI and the right supramarginal gyrus, as well as the PI and the right precentral/postcentral gyrus, was reduced in the T2DM group compared with the control group. In the T2DM group, we showed a significant negative correlation between glycated hemoglobin concentration and FC in the dAI and right hippocampus (r = −0.428, P = 0.001) after Bonferroni correction. We conclude that different insular subregions present distinct FC patterns with functional regions and that abnormal FC in these insular subregions may affect cognitive, emotional, and sensorimotor functions in patients with T2DM.

Neuroimaging Techniques in Advertising Research: Main Applications, Development, and Brain Regions and Processes

Despite the advancement in neuroimaging tools, studies about using neuroimaging tools to study the impact of advertising on brain regions and processes are scant and remain unclear in academic literature. In this article, we have followed a literature review methodology and a bibliometric analysis to select empirical and review papers that employed neuroimaging tools in advertising campaigns and to understand the global research trends in the neuromarketing domain. We extracted and analyzed sixty-three articles from the Web of Science database to answer our study questions. We found four common neuroimaging techniques employed in advertising research. We also found that the orbitofrontal cortex (OFC), the ventromedial prefrontal cortex, and the dorsolateral prefrontal cortex play a vital role in decision-making processes. The OFC is linked to positive valence, and the lateral OFC and left dorsal anterior insula related in negative valence. In addition, the thalamus and primary visual area associated with the bottom-up attention system, whereas the top-down attention system connected to the dorsolateral prefrontal cortex, parietal cortex, and primary visual areas. For memory, the hippocampus is responsible for generating and processing memories. We hope that this study provides valuable insights about the main brain regions and processes of interest for advertising.

Functional connectivity of the anterior insula during withdrawal from cigarette smoking.

Currently available therapies for smoking cessation have limited efficacy, and potential treatments that target specific brain regions are under evaluation, with a focus on the insula. The ventral and dorsal anterior subregions of the insula serve distinct functional networks, yet our understanding of how these subregions contribute to smoking behavior is unclear. Resting-state functional connectivity (RSFC) provides a window into network-level function associated with smoking-related internal states. The goal of this study was to determine potentially distinct relationships of ventral and dorsal anterior insula RSFC with cigarette withdrawal after brief abstinence from smoking. Forty-seven participants (24 women; 18-45 years old), who smoked cigarettes daily and were abstinent from smoking overnight (~12 h), provided self-reports of withdrawal and underwent resting-state fMRI before and after smoking the first cigarette of the day. Correlations between withdrawal and RSFC were computed separately for ventral and dorsal anterior insula seed regions in whole-brain voxel-wise analyses. Withdrawal was positively correlated with RSFC of the right ventral anterior insula and dorsal anterior cingulate cortex (dACC) before but not after smoking. The correlation was mainly due to a composite effect of craving and physical symptoms of withdrawal. These results suggest a role of right ventral anterior insula-dACC connectivity in the internal states that maintain smoking behavior (e.g., withdrawal) and present a specific neural target for brain-based therapies seeking to attenuate withdrawal symptoms in the critical early stages of smoking cessation.

Functional brain response to painful mechanical stimulation and painful stimulation in areas of secondary mechanical hyperalgesia: A meta-analysis

This study evaluated brain activity in response to painful and nonpainful mechanical stimuli within an area of secondary mechanical hyperalgesia (SMH) compared to non-sensitized areas. We performed a meta-analysis summarizing responses to three different types of stimuli. Furthermore, we summarize reported results of contrast maps comparing brain responses to mechanical stimuli in SMH that in non-sensitized regions. We investigated 3 categories of brain responses to 1) nonpainful mechanical stimuli in 226 participants across 16 studies, 2) painful mechanical stimuli in 164 participants across 11 studies, 3) mechanical stimuli in SMH in 84 participants across 7 studies, and 4) contrast maps of brain responses to mechanical stimuli in SMH versus painful mechanical stimuli in 107 participants across 7 studies. We used GingerALE 3.0.2 to create meta-analytic statistical parametric maps. We generated summary Z-maps by subtracting negative maps from positive maps. Maps were Z-value thresholded at 3.29 and a cluster size of 272 mm3. Nonpainful mechanical stimuli activated bilateral parietal operculum (PO), right inferior frontal gyrus (IFG) and inferior parietal lobule. Painful mechanical stimuli activated bilateral PO, bilateral IFG pars opercularis, and deactivation in bilateral superior occipital gyri. Mechanical stimuli in SMH activated bilateral PO, bilateral dorsal anterior insula, left postcentral gyrus and supragenual anterior cingulate cortex. The contrast of mechanical stimuli in SMH versus painful mechanical stimuli included greater activation in right thalamus, left lateral periaqueductal gray, right dorsolateral prefrontal (DLPFC), right Rolandic opercular, bilateral primary somatosensory, anterior midcingulate, and right middle insular cortices. Contrast results revealed greater activation during SMH compared to painful mechanical stimulation in right thalamus, right DLPFC, and left lateral periaqueductal gray. These areas are involved in pain modulation (hyperalgesic and analgesic), while responses in mid insula and mid cingulate cortices are prominent in processing salient and painful stimuli. Neurosurgery Pain Research Institute, Postdoctoral Scholarship (TJM). This study evaluated brain activity in response to painful and nonpainful mechanical stimuli within an area of secondary mechanical hyperalgesia (SMH) compared to non-sensitized areas. We performed a meta-analysis summarizing responses to three different types of stimuli. Furthermore, we summarize reported results of contrast maps comparing brain responses to mechanical stimuli in SMH that in non-sensitized regions. We investigated 3 categories of brain responses to 1) nonpainful mechanical stimuli in 226 participants across 16 studies, 2) painful mechanical stimuli in 164 participants across 11 studies, 3) mechanical stimuli in SMH in 84 participants across 7 studies, and 4) contrast maps of brain responses to mechanical stimuli in SMH versus painful mechanical stimuli in 107 participants across 7 studies. We used GingerALE 3.0.2 to create meta-analytic statistical parametric maps. We generated summary Z-maps by subtracting negative maps from positive maps. Maps were Z-value thresholded at 3.29 and a cluster size of 272 mm3. Nonpainful mechanical stimuli activated bilateral parietal operculum (PO), right inferior frontal gyrus (IFG) and inferior parietal lobule. Painful mechanical stimuli activated bilateral PO, bilateral IFG pars opercularis, and deactivation in bilateral superior occipital gyri. Mechanical stimuli in SMH activated bilateral PO, bilateral dorsal anterior insula, left postcentral gyrus and supragenual anterior cingulate cortex. The contrast of mechanical stimuli in SMH versus painful mechanical stimuli included greater activation in right thalamus, left lateral periaqueductal gray, right dorsolateral prefrontal (DLPFC), right Rolandic opercular, bilateral primary somatosensory, anterior midcingulate, and right middle insular cortices. Contrast results revealed greater activation during SMH compared to painful mechanical stimulation in right thalamus, right DLPFC, and left lateral periaqueductal gray. These areas are involved in pain modulation (hyperalgesic and analgesic), while responses in mid insula and mid cingulate cortices are prominent in processing salient and painful stimuli. Neurosurgery Pain Research Institute, Postdoctoral Scholarship (TJM).

Defining focal brain stimulation targets for PTSD using neuroimaging.

Focal brain stimulation has potential as a treatment for posttraumatic stress disorder (PTSD). In this review, we aim to inform selection of focal brain stimulation targets for treating PTSD by examining studies of the functional neuroanatomy of PTSD and treatment response. We first briefly review data on brain stimulation interventions for PTSD. Although published data suggest good efficacy overall, the neurobiological rationale for each stimulation target is not always clear. Therefore, we assess pre- and post-treatment (predominantly psychotherapy) functional neuroimaging studies in PTSD to determine which brain changes seem critical to treatment response. Results of these studies are presented within a previously proposed functional neural systems model of PTSD. While not completely consistent, research suggests that downregulating the fear learning and threat and salience detection circuits (i.e., amygdala, dorsal anterior cingulate cortex and insula) and upregulating the emotion regulation and executive function and contextual processing circuits (i.e., prefrontal cortical regions and hippocampus) may mediate PTSD treatment response. This literature review provides some justification for current focal brain stimulation targets. However, the examination of treatment effects on neural networks is limited, and studies that include the stimulation targets are lacking. Further, additional targets, such as the cingulate, medial prefrontal cortex, and inferior parietal lobe, may also be worth investigation, especially when considering how to achieve network level changes. Additional research combining PTSD treatment with functional neuroimaging will help move the field forward by identifying and validating novel targets, providing better rationale for specific treatment parameters and personalizing treatment for PTSD.

Cognitive Demands Influence Upper Extremity Motor Performance During Recovery From Acute Stroke.

To test the hypothesis that cognitive demands influence motor performance during recovery from acute stroke, we tested patients with acute stroke on 2 motor tasks with different cognitive demands and related task performance to cognitive impairment and neuroanatomic injury. We assessed the contralesional and ipsilesional upper extremities of a cohort of 50 patients with weakness after unilateral acute ischemic stroke at 3 time points with 2 tasks: the Box & Blocks Test, a task with greater cognitive demand, and Grip Strength, a simple and ballistic motor task. We compared performance on the 2 tasks, related motor performance to cognitive dysfunction, and used voxel-based lesion symptom mapping to determine neuroanatomic sites associated with motor performance. Consistent across contralesional and ipsilesional upper extremities and most pronounced immediately after stroke, Box & Blocks scores were significantly more impaired than Grip Strength scores. The presence of cognitive dysfunction significantly explained up to 33% of variance in Box & Blocks performance but was not associated with Grip Strength performance. While Grip Strength performance was associated with injury largely restricted to sensorimotor regions, Box & Blocks performance was associated with broad injury outside sensorimotor structures, particularly the dorsal anterior insula, a region known to be important for complex cognitive function. Together, these results suggest that cognitive demands influence upper extremity motor performance during recovery from acute stroke. Our findings emphasize the integrated nature of motor and cognitive systems and suggest that it is critical to consider cognitive demands during motor testing and neurorehabilitation after stroke.

Identifying neural signatures of tobacco retail outlet exposure: Preliminary validation of a “community neuroscience” paradigm

An extensive epidemiological literature indicates that increased exposure to tobacco retail outlets (TROs) places never smokers at greater risk for smoking uptake and current smokers at greater risk for increased consumption and smoking relapse. Yet research into the mechanisms underlying this effect has been limited. This preliminary study represents the first effort to examine the neurobiological consequences of exposure to personally relevant TROs among both smokers (n = 17) and nonsmokers (n = 17). Individuals carried a global positioning system (GPS) tracker for 2 weeks. Traces were used to identify TROs and control outlets that fell inside and outside their ideographically defined activity space. Participants underwent functional MRI (fMRI) scanning during which they were presented with images of these storefronts, along with similar store images from a different county and rated their familiarity with these stores. The main effect of activity space was additive with a Smoking status × Store type interaction, resulting in smokers exhibiting greater neural activation to TROs falling inside activity space within the parahippocampus, precuneus, medial prefrontal cortex, and dorsal anterior insula. A similar pattern was observed for familiarity ratings. Together, these preliminary findings suggest that the otherwise distinct neural systems involved in self-orientation/self-relevance and smoking motivation may act in concert and underlie TRO influence on smoking behavior. This study also offers a novel methodological framework for evaluating the influence of community features on neural activity that can be readily adapted to study other health behaviors.