Journal Articles

  • Identification of a direct GABAergic pallidocortical pathway in rodents EUROPEAN JOURNAL OF NEUROSCIENCE Chen, M. C., Ferrari, L., Sacchet, M. D., Foland-Ross, L. C., Qiu, M., Gotlib, I. H., Fuller, P. M., Arrigoni, E., Lu, J. 2015; 41 (6): 748-759


    Interaction between the basal ganglia and the cortex plays a critical role in a range of behaviors. Output from the basal ganglia to the cortex is thought to be relayed through the thalamus, but an intriguing alternative is that the basal ganglia may directly project to and communicate with the cortex. We explored an efferent projection from the globus pallidus externa (GPe), a key hub in the basal ganglia system, to the cortex of rats and mice. Anterograde and retrograde tracing revealed projections to the frontal premotor cortex, especially the deep projecting layers, originating from GPe neurons that receive axonal inputs from the dorsal striatum. Cre-dependent anterograde tracing in Vgat-ires-cre mice confirmed that the pallidocortical projection is GABAergic, and in vitro optogenetic stimulation in the cortex of these projections produced a fast inhibitory postsynaptic current in targeted cells that was abolished by bicuculline. The pallidocortical projections targeted GABAergic interneurons and, to a lesser extent, pyramidal neurons. This GABAergic pallidocortical pathway directly links the basal ganglia and cortex, and may play a key role in behavior and cognition in normal and disease states.

    View details for DOI 10.1111/ejn.12822

    View details for Web of Science ID 000351439000002

    View details for PubMedID 25581560

  • Attention Drives Synchronization of Alpha and Beta Rhythms between Right Inferior Frontal and Primary Sensory Neocortex. journal of neuroscience Sacchet, M. D., LaPlante, R. A., Wan, Q., Pritchett, D. L., Lee, A. K., Hmlinen, M., Moore, C. I., Kerr, C. E., Jones, S. R. 2015; 35 (5): 2074-2082


    The right inferior frontal cortex (rIFC) is specifically associated with attentional control via the inhibition of behaviorally irrelevant stimuli and motor responses. Similarly, recent evidence has shown that alpha (7-14 Hz) and beta (15-29 Hz) oscillations in primary sensory neocortical areas are enhanced in the representation of non-attended stimuli, leading to the hypothesis that allocation of these rhythms plays an active role in optimal inattention. Here, we tested the hypothesis that selective synchronization between rIFC and primary sensory neocortex occurs in these frequency bands during inattention. We used magnetoencephalography to investigate phase synchrony between primary somatosensory (SI) and rIFC regions during a cued-attention tactile detection task that required suppression of response to uncertain distractor stimuli. Attentional modulation of synchrony between SI and rIFC was found in both the alpha and beta frequency bands. This synchrony manifested as an increase in the alpha-band early after cue between non-attended SI representations and rIFC, and as a subsequent increase in beta-band synchrony closer to stimulus processing. Differences in phase synchrony were not found in several proximal control regions. These results are the first to reveal distinct interactions between primary sensory cortex and rIFC in humans and suggest that synchrony between rIFC and primary sensory representations plays a role in the inhibition of irrelevant sensory stimuli and motor responses.

    View details for DOI 10.1523/JNEUROSCI.1292-14.2015

    View details for PubMedID 25653364

  • Support vector machine classification of major depressive disorder using diffusion-weighted neuroimaging and graph theory. Frontiers in psychiatry Sacchet, M. D., Prasad, G., Foland-Ross, L. C., Thompson, P. M., Gotlib, I. H. 2015; 6: 21-?


    Recently, there has been considerable interest in understanding brain networks in major depressive disorder (MDD). Neural pathways can be tracked in the living brain using diffusion-weighted imaging (DWI); graph theory can then be used to study properties of the resulting fiber networks. To date, global abnormalities have not been reported in tractography-based graph metrics in MDD, so we used a machine learning approach based on "support vector machines" to differentiate depressed from healthy individuals based on multiple brain network properties. We also assessed how important specific graph metrics were for this differentiation. Finally, we conducted a local graph analysis to identify abnormal connectivity at specific nodes of the network. We were able to classify depression using whole-brain graph metrics. Small-worldness was the most useful graph metric for classification. The right pars orbitalis, right inferior parietal cortex, and left rostral anterior cingulate all showed abnormal network connectivity in MDD. This is the first use of structural global graph metrics to classify depressed individuals. These findings highlight the importance of future research to understand network properties in depression across imaging modalities, improve classification results, and relate network alterations to psychiatric symptoms, medication, and comorbidities.

    View details for DOI 10.3389/fpsyt.2015.00021

    View details for PubMedID 25762941

  • Activation of the medial prefrontal and posterior cingulate cortex during encoding of negative material predicts symptom worsening in major depression NEUROREPORT Foland-Ross, L. C., Hamilton, P., Sacchet, M. D., Furman, D. J., Sherdell, L., Gotlib, I. H. 2014; 25 (5): 324-329


    Considerable research indicates that depressed individuals have better memory for negative material than do nondepressed individuals, and that this bias is associated with differential patterns of neural activation. It is not known, however, whether these aberrant activation patterns predict illness course. Using functional neuroimaging, we examined whether change in depressive symptoms is predicted by baseline patterns of neural activation that underlie negative memory biases in major depressive disorder. Depressed participants viewed negative and neutral pictures during functional MRI at baseline and completed an incidental memory task for these pictures 1 week later. Depression severity was assessed by administering the Beck Depression Inventory both at baseline (Time 1) and at Time 2, an average of 18 months later. Contrast maps of activation for subsequently remembered negative versus subsequently remembered neutral pictures were regressed against change in Beck Depression Inventory scores between Time 1 and Time 2, controlling for initial symptom severity. Results from this analysis revealed no associations between memory sensitivity for negative stimuli and symptom change. In contrast, whole brain analyses revealed significant positive associations between within-subject changes in depressive symptoms and baseline neural activation to successfully recalled negative pictures in the posterior cingulate cortex and medial prefrontal cortex. These findings indicate that neural activation in cortical midline regions is a better predictor of long-term symptomatic outcome than is memory sensitivity for negative material.

    View details for DOI 10.1097/WNR.0000000000000095

    View details for Web of Science ID 000332601600009

    View details for PubMedID 24356105

  • Structural abnormality of the corticospinal tract in major depressive disorder. Biology of mood & anxiety disorders Sacchet, M. D., Prasad, G., Foland-Ross, L. C., Joshi, S. H., Hamilton, J. P., Thompson, P. M., Gotlib, I. H. 2014; 4: 8-?


    Scientists are beginning to document abnormalities in white matter connectivity in major depressive disorder (MDD). Recent developments in diffusion-weighted image analyses, including tractography clustering methods, may yield improved characterization of these white matter abnormalities in MDD. In this study, we acquired diffusion-weighted imaging data from MDD participants and matched healthy controls. We analyzed these data using two tractography clustering methods: automated fiber quantification (AFQ) and the maximum density path (MDP) procedure. We used AFQ to compare fractional anisotropy (FA; an index of water diffusion) in these two groups across major white matter tracts. Subsequently, we used the MDP procedure to compare FA differences in fiber paths related to the abnormalities in major fiber tracts that were identified using AFQ.FA was higher in the bilateral corticospinal tracts (CSTs) in MDD (p's?

    View details for DOI 10.1186/2045-5380-4-8

    View details for PubMedID 25295159

  • Major depression duration reduces appetitive word use: An elaborated verbal recall of emotional photographs JOURNAL OF PSYCHIATRIC RESEARCH Capecelatro, M. R., Sacchet, M. D., Hitchcock, P. F., Miller, S. M., Britton, W. B. 2013; 47 (6): 809-815


    Major depressive disorder (MDD) is characterized by cognitive biases in attention, memory and language use. Language use biases often parallel depression symptoms, and contain over-representations of both negative emotive and death words as well as low levels of positive emotive words. This study further explores cognitive biases in depression by comparing the effect of current depression status to cumulative depression history on an elaborated verbal recall of emotional photographs.Following a negative mood induction, fifty-two individuals (42 women) with partially-remitted depression viewed - then recalled and verbally described - slides from the International Affective Picture System (IAPS). Descriptions were transcribed and frequency of depression-related word use (positive emotion, negative emotion, sex, ingestion and death) was analyzed using the Linguistic Inquiry and Word Count program (LIWC).Contrary to expectations and previous findings, current depression status did not affect word use in any categories of interest. However, individuals with more than 5 years of previous depression used fewer words related to positive emotion (t(50)=2.10, p=.04, (d=0.57)), and sex (t(48)=2.50, p=.013 (d=0.81)), and there was also a trend for these individuals to use fewer ingestion words (t(50)=1.95, p=.057 (d=0.58)), suggesting a deficit in appetitive processing.Our findings suggest that depression duration affects appetitive information processing and that appetitive word use may be a behavioral marker for duration related brain changes which may be used to inform treatment.

    View details for DOI 10.1016/j.jpsychires.2013.01.022

    View details for Web of Science ID 000318328700016

    View details for PubMedID 23510497

  • Mindfulness starts with the body: somatosensory attention and top-down modulation of cortical alpha rhythms in mindfulness meditation FRONTIERS IN HUMAN NEUROSCIENCE Kerr, C. E., Sacchet, M. D., Lazar, S. W., Moore, C. I., Jones, S. R. 2013; 7


    Using a common set of mindfulness exercises, mindfulness based stress reduction (MBSR) and mindfulness based cognitive therapy (MBCT) have been shown to reduce distress in chronic pain and decrease risk of depression relapse. These standardized mindfulness (ST-Mindfulness) practices predominantly require attending to breath and body sensations. Here, we offer a novel view of ST-Mindfulness's somatic focus as a form of training for optimizing attentional modulation of 7-14 Hz alpha rhythms that play a key role in filtering inputs to primary sensory neocortex and organizing the flow of sensory information in the brain. In support of the framework, we describe our previous finding that ST-Mindfulness enhanced attentional regulation of alpha in primary somatosensory cortex (SI). The framework allows us to make several predictions. In chronic pain, we predict somatic attention in ST-Mindfulness "de-biases" alpha in SI, freeing up pain-focused attentional resources. In depression relapse, we predict ST-Mindfulness's somatic attention competes with internally focused rumination, as internally focused cognitive processes (including working memory) rely on alpha filtering of sensory input. Our computational model predicts ST-Mindfulness enhances top-down modulation of alpha by facilitating precise alterations in timing and efficacy of SI thalamocortical inputs. We conclude by considering how the framework aligns with Buddhist teachings that mindfulness starts with "mindfulness of the body." Translating this theory into neurophysiology, we hypothesize that with its somatic focus, mindfulness' top-down alpha rhythm modulation in SI enhances gain control which, in turn, sensitizes practitioners to better detect and regulate when the mind wanders from its somatic focus. This enhanced regulation of somatic mind-wandering may be an important early stage of mindfulness training that leads to enhanced cognitive regulation and metacognition.

    View details for DOI 10.3389/fnhum.2013.00012

    View details for Web of Science ID 000315343200001

    View details for PubMedID 23408771

  • Spatial smoothing systematically biases the localization of reward-related brain activity NEUROIMAGE Sacchet, M. D., Knutson, B. 2013; 66: 270-277
  • Mindfulness training alters emotional memory recall compared to active controls: support for an emotional information processing model of mindfulness FRONTIERS IN HUMAN NEUROSCIENCE Roberts-Wolfe, D., Sacchet, M., Hastings, E., Roth, H., Britton, W. 2012; 6


    Objectives: While mindfulness-based interventions have received widespread application in both clinical and non-clinical populations, the mechanism by which mindfulness meditation improves well-being remains elusive. One possibility is that mindfulness training alters the processing of emotional information, similar to prevailing cognitive models of depression and anxiety. The aim of this study was to investigate the effects of mindfulness training on emotional information processing (i.e., memory) biases in relation to both clinical symptomatology and well-being in comparison to active control conditions. Methods: Fifty-eight university students (28 female, age?=?20.1??2.7?years) participated in either a 12-week course containing a "meditation laboratory" or an active control course with similar content or experiential practice laboratory format (music). Participants completed an emotional word recall task and self-report questionnaires of well-being and clinical symptoms before and after the 12-week course. Results: Meditators showed greater increases in positive word recall compared to controls [F(1, 56)?=?6.6, p?=?0.02]. The meditation group increased significantly more on measures of well-being [F(1, 56)?=?6.6, p?=?0.01], with a marginal decrease in depression and anxiety [F(1, 56)?=?3.0, p?=?0.09] compared to controls. Increased positive word recall was associated with increased psychological well-being (r?=?0.31, p?=?0.02) and decreased clinical symptoms (r?=?-0.29, p?=?0.03). Conclusion: Mindfulness training was associated with greater improvements in processing efficiency for positively valenced stimuli than active control conditions. This change in emotional information processing was associated with improvements in psychological well-being and less depression and anxiety. These data suggest that mindfulness training may improve well-being via changes in emotional information processing. Future research with a fully randomized design will be needed to clarify the possible influence of self-selection.

    View details for DOI 10.3389/fnhum.2012.00015

    View details for Web of Science ID 000302181400001

    View details for PubMedID 22347856

  • Toward an affective neuroscience account of financial risk taking. Frontiers in neuroscience Wu, C. C., Sacchet, M. D., Knutson, B. 2012; 6: 159-?


    To explain human financial risk taking, economic, and finance theories typically refer to the mathematical properties of financial options, whereas psychological theories have emphasized the influence of emotion and cognition on choice. From a neuroscience perspective, choice emanates from a dynamic multicomponential process. Recent technological advances in neuroimaging have made it possible for researchers to separately visualize perceptual input, intermediate processing, and motor output. An affective neuroscience account of financial risk taking thus might illuminate affective mediators that bridge the gap between statistical input and choice output. To test this hypothesis, we conducted a quantitative meta-analysis (via activation likelihood estimate or ALE) of functional magnetic resonance imaging experiments that focused on neural responses to financial options with varying statistical moments (i.e., mean, variance, skewness). Results suggested that different statistical moments elicit both common and distinct patterns of neural activity. Across studies, high versus low mean had the highest probability of increasing ventral striatal activity, but high versus low variance had the highest probability of increasing anterior insula activity. Further, high versus low skewness had the highest probability of increasing ventral striatal activity. Since ventral striatal activity has been associated with positive aroused affect (e.g., excitement), whereas anterior insular activity has been associated with negative aroused affect (e.g., anxiety) or general arousal, these findings are consistent with the notion that statistical input influences choice output by eliciting anticipatory affect. The findings also imply that neural activity can be used to predict financial risk taking - both when it conforms to and violates traditional models of choice.

    View details for DOI 10.3389/fnins.2012.00159

    View details for PubMedID 23129993

  • Volitional control of neuromagnetic coherence. Frontiers in neuroscience Sacchet, M. D., Mellinger, J., Sitaram, R., Braun, C., Birbaumer, N., Fetz, E. 2012; 6: 189-?


    Coherence of neural activity between circumscribed brain regions has been implicated as an indicator of intracerebral communication in various cognitive processes. While neural activity can be volitionally controlled with neurofeedback, the volitional control of coherence has not yet been explored. Learned volitional control of coherence could elucidate mechanisms of associations between cortical areas and its cognitive correlates and may have clinical implications. Neural coherence may also provide a signal for brain-computer interfaces (BCI). In the present study we used the Weighted Overlapping Segment Averaging method to assess coherence between bilateral magnetoencephalograph sensors during voluntary digit movement as a basis for BCI control. Participants controlled an onscreen cursor, with a success rate of 124 of 180 (68.9%, sign-test p?

    View details for DOI 10.3389/fnins.2012.00189

    View details for PubMedID 23271991

  • Toward an affective neuroscience account of financial risk taking FRONTIERS IN NEUROSCIENCE Wu, C. C., Sacchet, M. D., Knutson, B. 2012; 6
  • Volitional control of neuromagnetic coherence FRONTIERS IN NEUROSCIENCE Sacchet, M. D., Mellinger, J., Sitaram, R., Braun, C., Birbaumer, N., Fetz, E. 2012; 6

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