Eric J. Waldron

Network measures predict neuropsychological outcome after brain injury

Significance Thought depends on the brain, and cognitive neuroscience has shown that different sets of brain regions (systems) support different cognitive abilities. We hypothesized that complex cognition might be especially supported by hub brain locations that participate in many such systems. We studied neurological patients with focal brain lesions, and found that damage to hub locations produced much greater cognitive impairment than damage to other locations. This work may improve the understanding of outcomes of brain injuries (from, e.g., stroke, resection, or trauma) and help inform prognosis and rehabilitation efforts. Hubs are network components that hold positions of high importance for network function. Previous research has identified hubs in human brain networks derived from neuroimaging data; however, there is little consensus on the localization of such hubs. Moreover, direct evidence regarding the role of various proposed hubs in network function (e.g., cognition) is scarce. Regions of the default mode network (DMN) have been frequently identified as “cortical hubs” of brain networks. On theoretical grounds, we have argued against some of the methods used to identify these hubs and have advocated alternative approaches that identify different regions of cortex as hubs. Our framework predicts that our proposed hub locations may play influential roles in multiple aspects of cognition, and, in contrast, that hubs identified via other methods (including salient regions in the DMN) might not exert such broad influence. Here we used a neuropsychological approach to directly test these predictions by studying long-term cognitive and behavioral outcomes in 30 patients, 19 with focal lesions to six “target” hubs identified by our approaches (high system density and participation coefficient) and 11 with focal lesions to two “control” hubs (high degree centrality). In support of our predictions, we found that damage to target locations produced severe and widespread cognitive deficits, whereas damage to control locations produced more circumscribed deficits. These findings support our interpretation of how neuroimaging-derived network measures relate to cognition and augment classic neuroanatomically based predictions about cognitive and behavioral outcomes after focal brain injury.

Volumetric vs. surface-based alignment for localization of auditory cortex activation.

The high degree of intersubject structural variability in the human brain is an obstacle in combining data across subjects in functional neuroimaging experiments. A common method for aligning individual data is normalization into standard 3D stereotaxic space. Since the inherent geometry of the cortex is that of a 2D sheet, higher precision can potentially be achieved if the intersubject alignment is based on landmarks in this 2D space. To examine the potential advantage of surface-based alignment for localization of auditory cortex activation, and to obtain high-resolution maps of areas activated by speech sounds, fMRI data were analyzed from the left hemisphere of subjects tested with phoneme and tone discrimination tasks. We compared Talairach stereotaxic normalization with two surface-based methods: Landmark Based Warping, in which landmarks in the auditory cortex were chosen manually, and Automated Spherical Warping, in which hemispheres were aligned automatically based on spherical representations of individual and average brains. Examination of group maps generated with these alignment methods revealed superiority of the surface-based alignment in providing precise localization of functional foci and in avoiding mis-registration due to intersubject anatomical variability. Human left hemisphere cortical areas engaged in complex auditory perception appear to lie on the superior temporal gyrus, the dorsal bank of the superior temporal sulcus, and the lateral third of Heschls gyrus.

Left posterior temporal regions are sensitive to auditory categorization

Recent studies suggest that the left superior temporal gyrus and sulcus (LSTG/S) play a role in speech perception, although the precise function of these areas remains unclear. Here, we test the hypothesis that regions in the LSTG/S play a role in the categorization of speech phonemes, irrespective of the acoustic properties of the sounds and prior experience of the listener with them. We examined changes in functional magnetic resonance imaging brain activation related to a perceptual shift from nonphonetic to phonetic analysis of sine-wave speech analogs. Subjects performed an identification task before scanning and a discrimination task during scanning with phonetic (P) and nonphonetic (N) sine-wave sounds, both before (Pre) and after (Post) being exposed to the phonetic properties of the P sounds. Behaviorally, experience with the P sounds induced categorical identification of these sounds. In the PostP > PreP and PostP > PostN contrasts, an area in the posterior LSTG/S was activated. For both P and N sounds, the activation in this region was correlated with the degree of categorical identification in individual subjects. The results suggest that these areas in the posterior LSTG/S are sensitive neither to the acoustic properties of speech nor merely to the presence of phonetic information, but rather to the listeners awareness of category representations for auditory inputs.

Attentional Modulation in the Detection of Irrelevant Deviance: A Simultaneous ERP/fMRI Study

Little is known about the neural mechanisms that control attentional modulation of deviance detection in the auditory modality. In this study, we manipulated the difficulty of a primary task to test the relation between task difficulty and the detection of infrequent, task-irrelevant deviant (D) tones (1300 Hz) presented among repetitive standard (S) tones (1000 Hz). Simultaneous functional magnetic resonance imaging (fMRI)/event-related potentials (ERPs) were recorded from 21 subjects performing a two-alternative forced-choice duration discrimination task (short and long tones of equal probability). The duration of the short tone was always 50 msec. The duration of the long tone was 100 msec in the easy task and 60 msec in the difficult task. As expected, response accuracy decreased and response time (RT) increased in the difficult compared with the easy task. Performance was also poorer for D than for S tones, indicating distraction by task-irrelevant frequency information on trials involving D tones. In the difficult task, an amplitude increase was observed in the difference waves for N1 and P3a, ERP components associated with increased attention to deviant sounds. The mismatch negativity (MMN) response, associated with passive deviant detection, was larger in the easy task, demonstrating the susceptibility of this component to attentional manipulations. The fMRI contrast D > S in the difficult task revealed activation on the right superior temporal gyrus (STG) and extending ventrally into the superior temporal sulcus, suggesting this regions involvement in involuntary attention shifting toward unattended, infrequent sounds. Conversely, passive deviance detection, as reflected by the MMN, was associated with more dorsal activation on the STG. These results are consistent with the view that the dorsal STG region is responsive to mismatches between the memory trace of the standard and the incoming deviant sound, whereas the ventral STG region is activated by involuntary shifts of attention to task-irrelevant auditory features.

fMRI of Past Tense Processing: The Effects of Phonological Complexity and Task Difficulty

The generation of regular and irregular past tense verbs has been an important issue in cognitive science and has been used to advance different models of the organization of language in the brain. The dual-system view holds that the regular past tense forms are generated by a rule while irregular forms are retrieved from memory. The single-system view, on the other hand, holds that both forms are generated by a single integrated system and differ only in their reliance on factors such as phonology and semantics. We conducted an event-related fMRI study to examine the activation patterns associated with the generation and reading of regular and irregular past tense forms, in addition to the reading of their stems. Regular and irregular past tense generation activated similar brain regions compared to the reading of their respective stems. The areas activated more for irregular generation compared to regular generation included inferior frontal, precentral, and parietal regions bilaterally. This activation can be interpreted as ref lecting the greater attentional and response selection demands of irregular generation. Compared to irregular generation, regular generation activated a small region in the left superior temporal gyrus when the regular and irregular past tense forms were mismatched on phonological complexity. No areas were more activated for regulars than irregulars when the past tense forms were matched on this variable. This suggests that the activation specific to regulars was related to the higher phonological complexity of their past tense forms rather than to their generation. A contrast of the reading of regular and irregular past tense forms was consistent with this hypothesis. These results support a single-system account of past tense generation.

The Neurological Outcome Scale for Traumatic Brain Injury (NOS-TBI): II. Reliability and Convergent Validity

A standardized measure of neurological dysfunction specifically designed for TBI currently does not exist and the lack of assessment of this domain represents a substantial gap. To address this, the Neurological Outcome Scale for Traumatic Brain Injury (NOS-TBI) was developed for TBI outcomes research through the addition to and modification of items specifically relevant to patients with TBI, based on the National Institutes of Health Stroke Scale. In a sample of 50 participants (mean age = 33.3 years, SD = 12.9) <or=18 months (mean = 3.1, SD = 3.2) following moderate (n = 8) to severe (n = 42) TBI, internal consistency of the NOS-TBI was high (Cronbachs alpha = 0.942). Test-retest reliability also was high (rho = 0.97, p < 0.0001), and individual item kappas between independent raters were excellent, ranging from 0.83 to 1.0. Overall inter-rater agreement between independent raters (Kendalls coefficient of concordance) for the NOS-TBI total score was excellent (W = 0.995). Convergent validity was demonstrated through significant Spearman rank-order correlations between the NOS-TBI and the concurrently administered Disability Rating Scale (rho = 0.75, p < 0.0001), Rancho Los Amigos Scale (rho = -0.60, p < 0.0001), Supervision Rating Scale (rho = 0.59, p < 0.0001), and the FIM (rho = -0.68, p < 0.0001). These results suggest that the NOS-TBI is a reliable and valid measure of neurological functioning in patients with moderate to severe TBI.

The role of age of acquisition on past tense generation in Spanish-English bilinguals: An fMRI study

At its most basic sense, the sensorimotor/emergentist (S/E) model suggests that early second language (L2) learning is preferentially reliant upon sensory and motor processes, while later L2 learning is accomplished by greater reliance on executive abilities. To investigate the S/E model using fMRI, neural correlates of L2 age of acquisition were examined by employing a past-tense generation task on 22 L2 proficient bilinguals. Early bilinguals preferentially recruited left hemisphere sensorimotor regions involved in motoric control and articulation. In contrast, later learners, to a greater degree, engaged regions involved in executive cognitive control and lexical access. The data support the notion that early L2 learners devote neural resources to motor control during lexical retrieval. In contrast, later L2 learners recruit executive control mechanisms to generate the past tense. These data are consistent with the S/E model of bilingual language learning, and serve as an extension of cognitive control theories.

Neuropsychological characterization of three adolescent females with anti-NMDA receptor encephalitis in the acute, post-acute, and chronic phases: an inter-institutional case series

Abstract Objective: Anti-N-methyl-D-aspartate (anti-NMDA) receptor encephalitis is an acute, immune-mediated paraneoplastic syndrome that often presents with psychobehavioral changes, abnormal movements, autonomic instability, seizures, and cognitive dysfunction. While the disease continues to be more readily identified and appropriately treated, the course of cognitive deficits from the acute to post-acute to chronic phase has not been well described, particularly in the pediatric population. This case series describes the neuropsychological functioning of three adolescent females with anti-NMDA receptor encephalitis from its early presentation to long-term follow-up.Method: All three cases are adolescent females with antibody-confirmed anti-NMDA receptor encephalitis. A review of the literature is provided summarizing the disorder and its known cognitive sequelae, pathophysiology, treatment, and prognostic factors, as well as each patient’s relevant history, symptom presentation, and disease course. Neuropsychological functioning of each patient was evaluated from her initial inpatient hospitalization to long-term follow-up (3.5–12 months after acute evaluation).Results: All three patients demonstrated clear improvement in cognitive functioning during the course of their recovery, though selected deficits in executive functioning, fine motor dexterity, language, and memory were observed at long-term follow-up in some of our patients.Conclusions: Findings are consistent with studies in adults that found cognitive deficits following anti-NMDA receptor encephalitis. Though gradual recovery was noted over time, all three patients reported no clinically significant difficulties during their final evaluation, despite showing mild impairment in some areas, emphasizing the importance of ongoing neuropsychological follow-up.

Brain Network Theory Can Predict Whether Neuropsychological Outcomes Will Differ from Clinical Expectations

Objective Theories of brain-network organization based on neuroimaging data have burgeoned in recent years, but the predictive power of such theories for cognition and behavior has only rarely been examined. Here, predictions from clinical neuropsychologists about the cognitive profiles of patients with focal brain lesions were used to evaluate a brain-network theory (Warren et al., 2014). Method Neuropsychologists made predictions regarding the neuropsychological profiles of a neurological patient sample (N = 30) based on lesion location. The neuropsychologists then rated the congruence of their predictions with observed neuropsychological outcomes, in regard to the “severity” of neuropsychological deficits and the “focality” of neuropsychological deficits. Based on the network theory, two types of lesion locations were identified: “target” locations (putative hubs in a brain-wide network) and “control” locations (hypothesized to play limited roles in network function). Results We found that patients with lesions of target locations (N = 19) had deficits of greater than expected severity that were more widespread than expected, whereas patients with lesions of control locations (N = 11) showed milder, circumscribed deficits that were more congruent with expectations. Conclusions The findings for the target brain locations suggest that prevailing views of brain–behavior relationships may be sharpened and refined by integrating recently proposed network-oriented perspectives.

Personality disturbances in amyotrophic lateral sclerosis: a case study demonstrating changes in personality without cognitive deficits.

Patients with amyotrophic lateral sclerosis (ALS) often show deficits on neuropsychological tests that tap functions related to the integrity of the prefrontal lobes. Various aspects of personality are also known to be mediated by prefrontal regions, particularly ventromedial prefrontal cortex (vmPFC). Other than apathy, personality changes have not been widely reported in patients with ALS, although clinical observations indicate such changes might be relatively common. Here, we report on a middle-aged woman with bulbar onset ALS (diagnosed 06/2011, examined in Spring, 2012) whose neuropsychological exam did not reveal cognitive deficits. She performed normally on tests of executive functioning. Self-report measures of mood and personality were unremarkable. However, significant personality changes subsequent to disease onset were reported by her husband and two daughters, and these changes were quantified with the Iowa Scales of Personality Change. Results show that personality disturbance may manifest in the absence of notable cognitive changes in ALS, and careful assessment of personality may be important for documenting early neurobehavioral changes in some ALS patients. Findings also show that patients with ALS may not have good insight into personality changes, underscoring the importance of acquiring collateral information. More generally, the results provide further evidence that ALS may compromise the integrity of ventromedial prefrontal regions.