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Thomas A. Zeffiro

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16 papers
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16

YNICL Journal 2020 Journal Article

Meta-analysis of brain metabolite differences in HIV infection

  • Lydia Chelala
  • Erin E. O'Connor
  • Peter B. Barker
  • Thomas A. Zeffiro

BACKGROUND: Numerous studies have used magnetic resonance spectroscopy (MRS) neurometabolite measurements to study HIV infection effects. While many have reported differences in total N-Acetylaspartate (tNAA), myo-Inositol (mI), and total Choline (tCho), there have been no meta-analyses performed to evaluate concordance across studies. PURPOSE: To evaluate the consistency of HIV serostatus effects on brain metabolites. STUDY SELECTION: The sample included studies conducted between 1993 and 2019 reporting HIV infection effects measured using proton MRS. tNAA/tCr ratios (21 papers), tCho/tCr ratios (21 papers), mI/tCr ratios (17 papers) and quantitative tCr (9 papers), sampling from basal ganglia (BG), gray matter (GM), and white matter (WM) were included. DATA ANALYSIS: Random effects meta-analysis using inverse variance weighting and bias corrected standardized mean differences (SMDs) was used. Meta-regression examined effects of publication year and data acquisition technique differences. DATA SYNTHESIS: ranged from 52 to 88% for the metabolite ratios. Both GM and WM tNAA/tCr SMDs were lower with increasing calendar year. LIMITATIONS: Many studies pooled participants with varying treatment, infection, and comorbidity durations. CONCLUSIONS: HIV neurometabolite studies showed consistently lower tNAA/tCr, higher tCho/tCr and higher mI/tCr ratios associated with chronic HIV infection. Substantial between-study variation may have resulted from measurement technique variations, study population differences and HIV treatment changes over time. Higher WM tCho/tCr and mI/tCr may reflect reactive gliosis or myelin turnover. Neurometabolite measurements can reliably detect chronic HIV infection effects and may be useful in understanding the pathophysiology of cognitive and sensorimotor decline following HIV infection. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence of neurometabolite differences in chronic HIV infection.

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YNICL Journal 2017 Journal Article

Parietal operculum and motor cortex activities predict motor recovery in moderate to severe stroke

  • Firdaus Fabrice Hannanu
  • Thomas A. Zeffiro
  • Laurent Lamalle
  • Olivier Heck
  • Félix Renard
  • Antoine Thuriot
  • Alexandre Krainik
  • Marc Hommel

While motor recovery following mild stroke has been extensively studied with neuroimaging, mechanisms of recovery after moderate to severe strokes of the types that are often the focus for novel restorative therapies remain obscure. We used fMRI to: 1) characterize reorganization occurring after moderate to severe subacute stroke, 2) identify brain regions associated with motor recovery and 3) to test whether brain activity associated with passive movement measured in the subacute period could predict motor outcome six months later. Because many patients with large strokes involving sensorimotor regions cannot engage in voluntary movement, we used passive flexion-extension of the paretic wrist to compare 21 patients with subacute ischemic stroke to 24 healthy controls one month after stroke. Clinical motor outcome was assessed with Fugl-Meyer motor scores (motor-FMS) six months later. Multiple regression, with predictors including baseline (one-month) motor-FMS and sensorimotor network regional activity (ROI) measures, was used to determine optimal variable selection for motor outcome prediction. Sensorimotor network ROIs were derived from a meta-analysis of arm voluntary movement tasks. Bootstrapping with 1000 replications was used for internal model validation. During passive movement, both control and patient groups exhibited activity increases in multiple bilateral sensorimotor network regions, including the primary motor (MI), premotor and supplementary motor areas (SMA), cerebellar cortex, putamen, thalamus, insula, Brodmann area (BA) 44 and parietal operculum (OP1-OP4). Compared to controls, patients showed: 1) lower task-related activity in ipsilesional MI, SMA and contralesional cerebellum (lobules V-VI) and 2) higher activity in contralesional MI, superior temporal gyrus and OP1-OP4. Using multiple regression, we found that the combination of baseline motor-FMS, activity in ipsilesional MI (BA4a), putamen and ipsilesional OP1 predicted motor outcome measured 6months later (adjusted-R2 =0. 85; bootstrap p<0. 001). Baseline motor-FMS alone predicted only 54% of the variance. When baseline motor-FMS was removed, the combination of increased activity in ipsilesional MI-BA4a, ipsilesional thalamus, contralesional mid-cingulum, contralesional OP4 and decreased activity in ipsilesional OP1, predicted better motor outcome (djusted-R2 =0. 96; bootstrap p<0. 001). In subacute stroke, fMRI brain activity related to passive movement measured in a sensorimotor network defined by activity during voluntary movement predicted motor recovery better than baseline motor-FMS alone. Furthermore, fMRI sensorimotor network activity measures considered alone allowed excellent clinical recovery prediction and may provide reliable biomarkers for assessing new therapies in clinical trial contexts. Our findings suggest that neural reorganization related to motor recovery from moderate to severe stroke results from balanced changes in ipsilesional MI (BA4a) and a set of phylogenetically more archaic sensorimotor regions in the ventral sensorimotor trend, in which OP1 and OP4 processes may complement the ipsilesional dorsal motor cortex in achieving compensatory sensorimotor recovery.

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YNICL Journal 2015 Journal Article

A greater involvement of posterior brain areas in interhemispheric transfer in autism: fMRI, DWI and behavioral evidences

  • Elise B. Barbeau
  • John D. Lewis
  • Julien Doyon
  • Habib Benali
  • Thomas A. Zeffiro
  • Laurent Mottron

A small corpus callosum (CC) is one of the most replicated neurobiological findings in autism spectrum (AS). However, its effect on interhemispheric (IH) communication is unknown. We combined structural (CC area and DWI), functional (task-related fMRI activation and connectivity analyses) as well as behavioral (Poffenberger and Purdue tasks) measures to investigate IH integration in adult AS individuals of typical intelligence. Despite similar behavioral IH transfer time and performances in bimanual tasks, the CC sub-regions connecting frontal and parietal cortical areas were smaller in AS than in non-AS individuals, while those connecting visual regions were similar. The activation of visual areas was lower in AS than in non-AS individuals during the presentation of visual stimuli. Behavioral IH performances were related to the properties of CC subregions connecting motor areas in non-AS individuals, but to the properties of posterior CC regions in AS individuals. Furthermore, there was greater functional connectivity between visual areas in the AS than in the non-AS group. Levels of connectivity were also stronger in visual than in motor regions in the autistic subjects, while the opposite was true for the non-autistic group. Thus, visual IH transfer plays an important role in visuo-motor tasks in AS individuals. These findings extend the well established enhanced role of perception in autistic cognition to visuo-motor IH information transfer.

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YNICL Journal 2015 Journal Article

Association of regional gray matter volumes in the brain with disruptive behavior disorders in male and female children

  • Kalina J. Michalska
  • Jean Decety
  • Thomas A. Zeffiro
  • Benjamin B. Lahey

Because the disruptive behavior disorders are highly impairing conditions, it is important to determine if structural variations in brain are associated early in life with these problems among children. Structural MRI data were acquired from 111 9-11 year olds (58 girls and 53 boys), 43 who met diagnostic criteria for oppositional defiant disorder and/or conduct disorder and 68 healthy controls. Voxel-based morphometry was used to examine associations of behavioral measures with gray matter volumes in whole-brain analyses. Unlike previous studies, variation in gray matter volume was not found to be associated with a disruptive behavior disorder diagnosis in any brain region at p < .05 with FWE correction. Nonetheless, an inverse nonlinear association of the number of conduct disorder (CD) symptoms with gray matter volume along the left superior temporal sulcus was significant in the full sample (p < .05 with FWE correction), with a trend in the right hemisphere (p < 0.001 uncorrected). There also was a trend toward a stronger association of the number of CD symptoms with gray matter volume along the left superior temporal sulcus in girls than boys. The present findings did not replicate previous findings of reduced gray matter volumes in the anterior insula, amygdala, and frontal cortex in youth with CD, but are consistent with previous findings of reduced gray matter volumes in temporal regions, particularly in girls.

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YNICL Journal 2015 Journal Article

Autistic fluid intelligence: Increased reliance on visual functional connectivity with diminished modulation of coupling by task difficulty

  • Isabelle Simard
  • David Luck
  • Laurent Mottron
  • Thomas A. Zeffiro
  • Isabelle Soulières

Different test types lead to different intelligence estimates in autism, as illustrated by the fact that autistic individuals obtain higher scores on the Raven's Progressive Matrices (RSPM) test than they do on the Wechsler IQ, in contrast to relatively similar performance on both tests in non-autistic individuals. However, the cerebral processes underlying these differences are not well understood. This study investigated whether activity in the fluid "reasoning" network, which includes frontal, parietal, temporal and occipital regions, is differently modulated by task complexity in autistic and non-autistic individuals during the RSPM. In this purpose, we used fMRI to study autistic and non-autistic participants solving the 60 RSPM problems focussing on regions and networks involved in reasoning complexity. As complexity increased, activity in the left superior occipital gyrus and the left middle occipital gyrus increased for autistic participants, whereas non-autistic participants showed increased activity in the left middle frontal gyrus and bilateral precuneus. Using psychophysiological interaction analyses (PPI), we then verified in which regions did functional connectivity increase as a function of reasoning complexity. PPI analyses revealed greater connectivity in autistic, compared to non-autistic participants, between the left inferior occipital gyrus and areas in the left superior frontal gyrus, right superior parietal lobe, right middle occipital gyrus and right inferior temporal gyrus. We also observed generally less modulation of the reasoning network as complexity increased in autistic participants. These results suggest that autistic individuals, when confronted with increasing task complexity, rely mainly on visuospatial processes when solving more complex matrices. In addition to the now well-established enhanced activity observed in visual areas in a range of tasks, these results suggest that the enhanced reliance on visual perception has a central role in autistic cognition.

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YNICL Journal 2015 Journal Article

Postural sway and regional cerebellar volume in adults with attention-deficit/hyperactivity disorder

  • Michael J. Hove
  • Thomas A. Zeffiro
  • Joseph Biederman
  • Zhi Li
  • Jeremy Schmahmann
  • Eve M. Valera

OBJECTIVE: Motor abnormalities, including impaired balance and increased postural sway, are commonly reported in children with ADHD, but have yet to be investigated in adults with ADHD. Furthermore, although these abnormalities are thought to stem from cerebellar deficits, evidence for an association between the cerebellum and these motor deficits has yet to be provided for either adults or children with ADHD. METHOD: In this study, we measured postural sway in adults with ADHD and controls, examining the relationship between sway and regional cerebellar gray matter volume. Thirty-two ADHD and 28 control participants completed various standing-posture tasks on a Wii balance board. RESULTS: Postural sway was significantly higher for the ADHD group compared to the healthy controls. Higher sway was positively associated with regional gray matter volume in the right posterior cerebellum (lobule VIII/IX). CONCLUSION: These findings show that sway abnormalities commonly reported in children with ADHD are also present in adults, and for the first time show a relationship between postural control atypicalities and the cerebellum in this group. Our findings extend the literature on motor abnormalities in ADHD and contribute to our knowledge of their neural substrate.

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YNIMG Journal 2008 Journal Article

Event-related single-shot volumetric functional magnetic resonance inverse imaging of visual processing

  • Fa-Hsuan Lin
  • Thomas Witzel
  • Joseph B. Mandeville
  • Jonathan R. Polimeni
  • Thomas A. Zeffiro
  • Douglas N. Greve
  • Graham Wiggins
  • Lawrence L. Wald

Developments in multi-channel radio-frequency (RF) coil array technology have enabled functional magnetic resonance imaging (fMRI) with higher degrees of spatial and temporal resolution. While modest improvement in temporal acceleration has been achieved by increasing the number of RF coils, the maximum attainable acceleration in parallel MRI acqisition is intrinsically limited only by the amount of independent spatial information in the combined array channels. Since the geometric configuration of a large-n MRI head coil array is similar to that used in EEG electrode or MEG SQUID sensor arrays, the source localization algorithms used in MEG or EEG source imaging can be extended to also process MRI coil array data, resulting in greatly improved temporal resolution by minimizing k-space traversal during signal acquisition. Using a novel approach, we acquire multi-channel MRI head coil array data and then apply inverse reconstruction methods to obtain volumetric fMRI estimates of blood oxygenation level dependent (BOLD) contrast at unprecedented whole-brain acquisition rates of 100 ms. We call this combination of techniques magnetic resonance Inverse Imaging (InI), a method that provides estimates of dynamic spatially-resolved signal change that can be used to construct statistical maps of task-related brain activity. We demonstrate the sensitivity and inter-subject reliability of volumetric InI using an event-related design to probe the hemodynamic signal modulations in primary visual cortex. Robust results from both single subject and group analyses demonstrate the sensitivity and feasibility of using volumetric InI in high temporal resolution investigations of human brain function.

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YNIMG Journal 2008 Journal Article

Linear constraint minimum variance beamformer functional magnetic resonance inverse imaging

  • Fa-Hsuan Lin
  • Thomas Witzel
  • Thomas A. Zeffiro
  • John W. Belliveau

Accurate estimation of the timing of neural activity is required to fully model the information flow among functionally specialized regions whose joint activity underlies perception, cognition and action. Attempts to detect the fine temporal structure of task-related activity would benefit from functional imaging methods allowing higher sampling rates. Spatial filtering techniques have been used in magnetoencephalography source imaging applications. In this work, we use the linear constraint minimal variance (LCMV) beamformer localization method to reconstruct single-shot volumetric functional magnetic resonance imaging (fMRI) data using signals acquired simultaneously from all channels of a high density radio-frequency (RF) coil array. The LCMV beamformer method generalizes the existing volumetric magnetic resonance inverse imaging (InI) technique, achieving higher detection sensitivity while maintaining whole-brain spatial coverage and 100 ms temporal resolution. In this paper, we begin by introducing the LCMV reconstruction formulation and then quantitatively assess its performance using both simulated and empirical data. To demonstrate the sensitivity and inter-subject reliability of volumetric LCMV InI, we employ an event-related design to probe the spatial and temporal properties of task-related hemodynamic signal modulations in primary visual cortex. Compared to minimum-norm estimate (MNE) reconstructions, LCMV offers better localization accuracy and superior detection sensitivity. Robust results from both single subject and group analyses demonstrate the excellent sensitivity and specificity of volumetric InI in detecting the spatial and temporal structure of task-related brain activity.

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YNIMG Journal 2003 Journal Article

Multivariate analysis of neuronal interactions in the generalized partial least squares framework: simulations and empirical studies

  • Fa-Hsuan Lin
  • Anthony R. McIntosh
  • John A. Agnew
  • Guinevere F. Eden
  • Thomas A. Zeffiro
  • John W. Belliveau

Identification of spatiotemporal interactions within/between neuron populations is critical for detection and characterization of large-scale neuronal interactions underlying perception, cognition, and behavior. Univariate analysis has been employed successfully in many neuroimaging studies. However, univariate analysis does not explicitly test for interactions between distributed areas of activity and is not sensitive to distributed responses across the brain. Multivariate analysis can explicitly test for multiple statistical models, including the designed paradigm, and allows for spatial and temporal model detection. Here, we investigate multivariate analysis approaches that take into consideration the 4D (time and space) covariance structure of the data. Principal component analysis (PCA) and independent component analysis (ICA) are two popular multivariate approaches with distinct mathematical constraints. Common difficulties in using these two different decompositions include the following: classification of the revealed components (task-related signal versus noise), overall signal-to-noise sensitivity, and the relatively low computational efficiency (multivariate analysis requires the entire raw data set and more time for model identification analysis). Using both Monte Carlo simulations and empirical data, we derived and tested the generalized partial least squares (gPLS) framework, which can incorporate both PCA and ICA decompositions with computational efficiency. The gPLS method explicitly incorporates the experimental design to simplify the identification of characteristic spatiotemporal patterns. We performed parametric modeling studies of a blocked-design experiment under various conditions, including background noise distribution, sampling rate, and hemodynamic response delay. We used a randomized grouping approach to manipulate the degrees of freedom of PCA and ICA in gPLS to characterize both paradigm coherent and transient brain responses. Simulation data suggest that in the gPLS framework, PCA mostly outperforms ICA as measured by the receiver operating curves (ROCs) in SNR from 0. 01 to 100, the hemodynamic response delays from 0 to 3 TR in fMRI, background noise models of Guassian, sub-Gaussian, and super-Gaussian distributions and the number of observations from 5, 10, to 20 in each block of a six-block experiment. Further, due to selective averaging, the gPLS method performs robustly in low signal-to-noise ratio (<1) experiments. We also tested PCA and ICA using PLS in a simulated event-related fMRI data to show their similar detection. Finally, we tested our gPLS approach on empirical fMRI motor data. Using the randomized grouping method, we are able to identify both transient responses and consistent paradigm/model coherent components in the 10-epoch block design motor fMRI experiment. Overall, studies of synthetic and empirical data suggest that PLS analysis, using PCA decomposition, provides a stable and powerful tool for exploration of fMRI/behavior data.

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YNIMG Journal 2002 Journal Article

Meta-Analysis of the Functional Neuroanatomy of Single-Word Reading: Method and Validation

  • Peter E. Turkeltaub
  • Guinevere F. Eden
  • Karen M. Jones
  • Thomas A. Zeffiro

Intersubject variability and subtle differences in experimental design can lead to variable results in studies of cognitive processes such as reading. To accurately identify the neural processes associated with cognition and sensorimotor processing, meta-analytic methods capable of identifying areas of consistent activation among studies are useful. This paper describes a novel approach for combining published neuroimaging results from multiple studies, designed to maximize the quantification of interstudy concordance while minimizing the subjective aspects of meta-analysis. In this method, a localization probability distribution was modeled for each activation focus obtained from 11 PET studies of reading single words aloud, and the union of these distributions was taken to yield an activation likelihood estimate map for the brain. Significance was assessed via permutation analysis of randomly generated sets of foci. Regions of significant concordance were identified in bilateral motor and superior temporal cortices, pre-SMA, left fusiform gyrus, and the cerebellum. These meta-analytic results were validated by comparison with new fMRI data on aloud word reading in normal adult subjects. Excellent correspondence between the two statistical maps was observed, with fMRI maxima lying close to all meta-analysis peaks and statistical values at the peaks identified by the two techniques correlating strongly. This close correspondence between PET meta-analysis and fMRI results also demonstrates the validity of using fMRI for the study of language tasks involving overt speech responses. Advantages of this automated meta-analysis technique include quantification of the level of concordance at all brain locations and the provision for use of a threshold for statistical significance of concordance.

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YNIMG Journal 1996 Journal Article

Locating the Motor Cortex on the MRI with Transcranial Magnetic Stimulation and PET

  • Eric M. Wassermann
  • Binseng Wang
  • Thomas A. Zeffiro
  • Norihiro Sadato
  • Alvaro Pascual-Leone
  • Camilo Toro
  • Mark Hallett

Transcranial magnetic stimulation with a focal coil was used to map the cortical representation of a hand muscle in four healthy subjects. In each subject, the three-dimensional locations of the magnetic stimulation positions and about 400 positions on the surface of the head were digitized. The amplitude-weighted center of gravity of each subject's map was found, and a line perpendicular to the local head surface was projected inward. The digitized heads were registered with the subjects' MRIs using the scalp contours. The coordinate transformations yielded by this process were used to map the stimulation positions and the perpendicular line into the MRIs. Brain areas imaged with positron emission tomography (PET) and15O-labeled water, activated by movement of the same muscle, were registered with the MRIs using the brain contours. In all cases, the magnetic stimulation lines encountered the surface of the brain at the anterior lip of the central sulcus and ran along the precentral gyrus a few millimeters anterior to the central sulcus, coming within 5–22 mm of all the PET activation maxima. This technique demonstrates the accuracy of transcranial magnetic stimulation for locating the primary motor area.

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YNIMG Journal 1996 Journal Article

The Visual Deficit Theory of Developmental Dyslexia

  • Guinevere F. Eden
  • John W. VanMeter
  • Judith M. Rumsey
  • Thomas A. Zeffiro

Dyslexia is an impairment in reading that can result from an abnormal developmental process in the case of developmental dyslexia or cerebral insult in the case of acquired dyslexia. It has long been known that the clinical manifestations of developmental dyslexia are varied. In addition to their reading difficulties, individuals with developmental dyslexia exhibit impairments in their ability to process the phonological features of written or spoken language. Recently, it has been demonstrated with a variety of experimental approaches that these individuals are also impaired on a number of visual tasks involving visuomotor, visuospatial, and visual motion processing. The results of these studies, as well as the anatomical and physiological anomalies seen in the brains of individuals with dyslexia, suggest that the pathophysiology of developmental dyslexia is more complex than originally thought, extending beyond the classically defined language areas of the brain. Functional neuroimaging is a useful tool to more precisely delineate the pathophysiology of this reading disorder.

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v2026.09.13