Brett E Youngerman

Weill Cornell Medical College, New York, New York, United States

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Publications (7)41.24 Total impact

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    ABSTRACT: Approximately 10% of patients with obsessive-compulsive disorder (OCD) have symptoms that are refractory to pharmacologic and cognitive-behavioral therapies. Neurosurgical interventions can be effective therapeutic options in these patients, but not all individuals respond. The mechanisms underlying this response variability are poorly understood. To identify neuroanatomical characteristics on preoperative imaging that differentiate responders from nonresponders to dorsal anterior cingulotomy, a neurosurgical lesion procedure used to treat refractory OCD. We retrospectively analyzed preoperative T1 and diffusion magnetic resonance imaging sequences from 15 patients (9 men and 6 women) who underwent dorsal anterior cingulotomy. Eight of the 15 patients (53%) responded to the procedure. We used voxel-based morphometry (VBM) and diffusion tensor imaging to identify structural and connectivity variations that could differentiate eventual responders from nonresponders. The VBM and probabilistic tractography metrics were correlated with clinical response to the cingulotomy procedure as measured by changes in the Yale-Brown Obsessive Compulsive Scale score. Voxel-based morphometry analysis revealed a gray matter cluster in the right anterior cingulate cortex, anterior to the eventual lesion, for which signal strength correlated with poor response (P = .017). Decreased gray matter in this region of the dorsal anterior cingulate cortex predicted improved response (mean [SD] gray matter partial volume for responders vs nonresponders, 0.47 [0.03] vs 0.66 [0.03]; corresponding to mean Yale-Brown Obsessive Compulsive Scale score change, -60% [19] vs -11% [9], respectively). Hemispheric asymmetry in connectivity between the eventual lesion and the caudate (for responders vs nonresponders, mean [SD] group laterality for individual lesion seeds, -0.79 [0.18] vs -0.08 [0.65]; P = .04), putamen (-0.55 [0.35] vs 0.50 [0.33]; P = .001), thalamus (-0.82 [0.19] vs 0.41 [0.24]; P = .001), pallidum (-0.78 [0.18] vs 0.43 [0.48]; P = .001), and hippocampus (-0.66 [0.33] vs 0.33 [0.18]; P = .001) also correlated significantly with clinical response, with increased right-sided connectivity predicting greater response. We identified features of anterior cingulate cortex structure and connectivity that predict clinical response to dorsal anterior cingulotomy for refractory OCD. These results suggest that the variability seen in individual responses to a highly consistent, stereotyped procedure may be due to neuroanatomical variation in the patients. Furthermore, these variations may allow us to predict which patients are most likely to respond to cingulotomy, thereby refining our ability to individualize this treatment for refractory psychiatric disorders.
    JAMA Psychiatry 12/2014; 72(2). DOI:10.1001/jamapsychiatry.2014.2216 · 12.01 Impact Factor
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    ABSTRACT: BACKGROUND AND PURPOSE: Level of consciousness is frequently assessed by command-following ability in the clinical setting. However, it is unclear what brain circuits are needed to follow commands. We sought to determine what networks differentiate command following from noncommand following patients after hemorrhagic stroke. METHODS: Structural MRI, resting-state functional MRI, and electroencephalography were performed on 25 awake and unresponsive patients with acute intracerebral and subarachnoid hemorrhage. Structural injury was assessed via volumetric T1-weighted MRI analysis. Functional connectivity differences were analyzed against a template of standard resting-state networks. The default mode network (DMN) and the task-positive network were investigated using seed-based functional connectivity. Networks were interrogated by pairwise coherence of electroencephalograph leads in regions of interest defined by functional MRI. RESULTS: Functional imaging of unresponsive patients identified significant differences in 6 of 16 standard resting-state networks. Significant voxels were found in premotor cortex, dorsal anterior cingulate gyrus, and supplementary motor area. Direct interrogation of the DMN and task-positive network revealed loss of connectivity between the DMN and the orbitofrontal cortex and new connections between the task-positive network and DMN. Coherence between electrodes corresponding to right executive network and visual networks was also decreased in unresponsive patients. CONCLUSIONS: Resting-state functional MRI and electroencephalography coherence data support a model in which multiple, chiefly frontal networks are required for command following. Loss of DMN anticorrelation with task-positive network may reflect a loss of inhibitory control of the DMN by motor-executive regions. Frontal networks should thus be a target for future investigations into the mechanism of responsiveness in the intensive care unit environment.
    Stroke 12/2014; DOI:10.1161/STROKEAHA.114.007645 · 6.02 Impact Factor
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    ABSTRACT: An almost sinusoidal, large amplitude ~0.1 Hz oscillation in cortical hemodynamics has been repeatedly observed in species ranging from mice to humans. However, the occurrence of 'slow sinusoidal hemodynamic oscillations' (SSHOs) in human functional magnetic resonance imaging (fMRI) studies is rarely noted or considered. As a result, little investigation into the cause of SSHOs has been undertaken, and their potential to confound fMRI analysis, as well as their possible value as a functional biomarker has been largely overlooked. Here, we report direct observation of large-amplitude, sinusoidal ~0.1 Hz hemodynamic oscillations in the cortex of an awake human undergoing surgical resection of a brain tumor. Intraoperative multispectral optical intrinsic signal imaging (MS-OISI) revealed that SSHOs were spatially localized to distinct regions of the cortex, exhibited wave-like propagation, and involved oscillations in the diameter of specific pial arterioles, confirming that the effect was not the result of systemic blood pressure oscillations. fMRI data collected from the same subject 4 days prior to surgery demonstrates that ~0.1 Hz oscillations in the BOLD signal can be detected around the same region. Intraoperative optical imaging data from a patient undergoing epilepsy surgery, in whom sinusoidal oscillations were not observed, is shown for comparison. This direct observation of the '0.1 Hz wave' in the awake human brain, using both intraoperative imaging and pre-operative fMRI, confirms that SSHOs occur in the human brain, and can be detected by fMRI. We discuss the possible physiological basis of this oscillation and its potential link to brain pathologies, highlighting its relevance to resting-state fMRI and its potential as a novel target for functional diagnosis and delineation of neurological disease.
    NeuroImage 10/2013; 87. DOI:10.1016/j.neuroimage.2013.10.044 · 6.13 Impact Factor
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    ABSTRACT: Substantia nigra neurons are known to play a key role in normal cognitive processes and disease states. While animal models and neuroimaging studies link dopamine neurons to novelty detection, this has not been demonstrated electrophysiologically in humans. We used single neuron extracellular recordings in awake human subjects undergoing surgery for Parkinson disease to characterize the features and timing of this response in the substantia nigra. We recorded 49 neurons in the substantia nigra. Using an auditory oddball task, we showed that they fired more rapidly following novel sounds than repetitive tones. The response was biphasic with peaks at approximately 250ms, comparable to that described in primate studies, and a second peak at 500ms. This response was primarily driven by slower firing neurons as firing rate was inversely correlated to novelty response. Our data provide human validation of the purported role of dopamine neurons in novelty detection and suggest modifications to proposed models of novelty detection circuitry.
    Brain research 10/2013; 1542. DOI:10.1016/j.brainres.2013.10.033 · 2.83 Impact Factor
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    ABSTRACT: While a tumour in or abutting primary motor cortex leads to motor weakness, how tumours elsewhere in the frontal or parietal lobes affect functional connectivity in a weak patient is less clear. We hypothesized that diminished functional connectivity in a distributed network of motor centres would correlate with motor weakness in subjects with brain masses. Furthermore, we hypothesized that interhemispheric connections would be most vulnerable to subtle disruptions in functional connectivity. We used task-free functional magnetic resonance imaging connectivity to probe motor networks in control subjects and patients with brain tumours (n = 22). Using a control dataset, we developed a method for automated detection of key nodes in the motor network, including the primary motor cortex, supplementary motor area, premotor area and superior parietal lobule, based on the anatomic location of the hand-motor knob in the primary motor cortex. We then calculated functional connectivity between motor network nodes in control subjects, as well as patients with and without brain masses. We used this information to construct weighted, undirected graphs, which were then compared to variables of interest, including performance on a motor task, the grooved pegboard. Strong connectivity was observed within the identified motor networks between all nodes bilaterally, and especially between the primary motor cortex and supplementary motor area. Reduced connectivity was observed in subjects with motor weakness versus subjects with normal strength (P < 0.001). This difference was driven mostly by decreases in interhemispheric connectivity between the primary motor cortices (P < 0.05) and between the left primary motor cortex and the right premotor area (P < 0.05), as well as other premotor area connections. In the subjects without motor weakness, however, performance on the grooved pegboard did not relate to interhemispheric connectivity, but rather was inversely correlated with connectivity between the left premotor area and left supplementary motor area, for both the left and the right hands (P < 0.01). Finally, two subjects who experienced severe weakness following surgery for their brain tumours were followed longitudinally, and the subject who recovered showed reconstitution of her motor network at follow-up. The subject who was persistently weak did not reconstitute his motor network. Motor weakness in subjects with brain tumours that do not involve primary motor structures is associated with decreased connectivity within motor functional networks, particularly interhemispheric connections. Motor networks become weaker as the subjects become weaker, and may become strong again during motor recovery.
    Brain 03/2012; 135(Pt 4):1017-26. DOI:10.1093/brain/aws041 · 10.23 Impact Factor
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    ABSTRACT: The limitations of intravenous thrombolysis therapy have paved the way for the development of novel endovascular technologies for use in the setting of acute stroke. These technologies range from direct intraarterial thrombolysis to various thrombus disruption or retrieval devices to angioplasty and stenting. The tools in the armamentarium of the neuroendovascular interventionalist enable fast, effective revascularization to be offered to a wider population of patients that may otherwise have few therapeutic options available to them. In this paper, we review the current state-of-the-art in neuroendovascular intervention for acute ischemic stroke. Particular emphasis is placed on delineating the indications and outcomes for use of these various technologies.
    International Journal of Stroke 12/2011; 6(6):511-22. DOI:10.1111/j.1747-4949.2011.00670.x · 4.03 Impact Factor
  • Brett E Youngerman, Guy M McKhann

Publication Stats

26 Citations
41.24 Total Impact Points

Institutions

  • 2014
    • Weill Cornell Medical College
      • Department of Radiology
      New York, New York, United States
  • 2011–2014
    • Columbia University
      • Department of Neurological Surgery
      New York, New York, United States