Hemispheric Regions Of Interest Research Articles

Reduced Gray Matter Volumes among Long Term Survivors of Head and Neck Cancer Treated with Radiation Therapy

<h3>Purpose/Objective(s)</h3> To investigate brain morphometry among long term survivors of head and neck cancer (HNC) treated with radiotherapy (RT). Specifically, we sought to calculate the brain age gap estimation among HNC survivors and to perform voxel-based morphometry (VBM) to calculate local gray matter volumes between HNC survivors and controls without history of cancer. <h3>Materials/Methods</h3> We recruited 39 HNC survivors (age range: 32.6y – 71.9y, 25.6% female) who were treated with RT >2y prior and who were currently without evidence of recurrent tumor. Participants underwent a multimodal magnetic resonance imaging (MRI) protocol. Scans were performed on a technology company's Prisma 3-Tesla using a 20-channel head coil. The scan protocol included T1-weighted imaging acquired at 1mm slice thickness. Brain age was estimated utilizing total brain gray matter, white matter, and cerebrospinal fluid with brainageR v2.1 and compared to chronologic age using the paired-samples T-test. VBM analysis was performed using Computational Anatomy Toolbox v12 with a regions of interest (ROI) approach utilizing the neuromorphometrics brain atlas. Gray matter volumes for ROIs were used to compare the study cohort to a normative sample of 35 adults age >45 years from the MGH-USC Human Connectome Project. Differences in gray matter volume were compared using the independent samples T-test controlled for total intracranial volume and sex and conservatively adjusted for multiple comparisons using the Holm-Bonferroni method. <h3>Results</h3> Estimated brain age was calculated for all participants; 1 participant was excluded from VBM analysis due to inadequate imaging quality. The mean estimated gray matter brain age of 60.2y was not significantly different to the mean chronologic age of the sample at 61.2y (p=0.353). Results from the VBM analysis demonstrated significantly reduced gray matter volume in the HNC survivors group compared to control group in the bilateral orbital gyrus, cingulate cortex, basal forebrain, thalamus, and cerebellum. In total, 35 left hemisphere regions of interest (ROIs) and 34 right hemisphere ROIs demonstrated reduced gray matter volume in the HNC survivor group at the p<0.001 significance level. No ROIs had increased gray matter among HNC survivors. <h3>Conclusion</h3> To our knowledge, this study is the first to assess brain morphometry among HNC survivors. We did not observe a brain age gap, but VBM gray matter volumes were significantly reduced in multiple brain regions, mostly subcortical and in the most inferior part of the cortex. Future research is needed to characterize how brain morphometry is related to patient outcomes as well as modifiable treatment factors such as brain radiation exposure.

Functional Deficits and Structural Changes Associated With the Visual Attention Network During Resting State in Adult Strabismic and Anisometropic Amblyopes.

Our previous study has shown impaired blood oxygen level-dependent (BOLD)/functional magnetic resonance imaging (fMRI) activation of the visual attention network in strabismic amblyopia (SA). However, there has been no comparison of resting state fMRI activation and functional connectivity (FC) in brain regions of interest (ROIs) along the visual attention network including visual cortex (V1), intraparietal sulcus (IPS), and frontal eye fields (FEFs) during closed eye resting across the SA (n = 20, 13LE), or anisometropic amblyopes (AA) (n = 20, 13LE) groups. Hence, we compared, gray matter volume (GMV), amplitude of low frequency fluctuations (ALFFs), regional homogeneity (ReHo), and FC in the left and right hemisphere ROIs of the visual attention network in SA, AA, and healthy controls (HCs) (n = 21). Correlation analyses of corrected visual acuity (cVA) of amblyopic eye and MRI results were also performed and showed that the LogMAR cVA of the amblyopic eye positively correlated with right zALFF and zReHo FEF of SA and right IPS of AA only. GMV of both left and right hemisphere V1 areas was significantly greater but ALFF was significantly lower for SA compared to AA and HC groups. zALFF and zReHo analyses in the AA and SA groups indicated significantly higher activation than that in the HC group in the right FEF and IPS but lower than that in the HC group in the left FEF, and only the SA group showed lower activation in both V1 areas than the HC group. FC values of the right FEF–left V1, right FEF–right V1, and right FEF–right IPS pathways in the SA and AA groups were also significantly higher than those in the HC group whereas all other FC values were non-significant. Thus, this study indicates that even during resting-state the visual attention network function is impaired in SA and AA participants with only right hemisphere FEF showing significant activation in SA and IPS in AA suggesting that the slower saccade activation times characteristic of amblyopic eyes lead to the dominant eye controlling activation of the visual attention network.

S137. LEFT HEMISPHERE MEG DEFICIT IN PITCH AND DURATION MISMATCH NEGATIVITY IN FIRST EPISODE PSYCHOSIS

BackgroundMismatch negativity (MMN) is an event-related potential (ERP) that is severely impaired in long-term schizophrenia. However, though largely debated, numerous electroencephalography (EEG) studies suggest that MMN is less reduced in individuals at their first episode of psychosis (FEP). Pitch MMN (pMMN) is not reduced, although duration MMN (dMMN) may be reduced compared to healthy controls (HC), and may show left hemisphere deficits early on. Few MMN studies in FEP have utilized magnetoencephalography (MEG). MEG could potentially be more sensitive to circumscribed differences, given its ability to more effectively localize MMN sources within the auditory cortex. Using MEG, we compared pMMN and dMMN between FEP and HC to identify potential source location- and timing-dependent differences in early disease course.MethodsSimultaneous MEG and EEG recordings of pMMN and dMMN were obtained with an oddball paradigm from 15 FEP and 19 HC. Of those, 12 FEP and 11 HC had usable EEG recordings, with the remainder lost due to a circuit board failure. MMN was calculated by subtraction of the sensor-space average to the standard tones from the average to the deviant tones. For EEG, mean amplitudes across fronto-central electrodes (F1, Fz, F2, FC1, FCz, FC2) were calculated over a 30 msec window at group peak latency. For MEG data, source activity was determined in Brainstorm using minimum norm estimation, multisphere head models, and individual MRI cortical surface reconstructions. Using the HCP Brain Atlas, regions of interest (ROIs) were determined based on areas of peak activity at two time windows for each task: an Early time window of 105–115 ms for both pMMN and dMMN, and a Late time window of 125–135 ms for pMMN and 155–165 ms for dMMN. Mean amplitudes were calculated over six auditory cortex ROIs: A1, Brodmann’s Area 43, Brodmann’s Area 52, Lateral Belt, Medial Belt, and Parabelt. Mixed-model ANOVA was then used to compare groups, regions, hemispheres, time windows, and tasks using SPSS software.ResultsFor EEG peak MMNs, there were no significant differences between groups in pMMN or dMMN (p’s > 0.1). For MEG sources, however, ANOVA indicated a Region x Hemisphere x Group interaction (p = 0.038), but no significant regional differences between Pitch and Duration or for either Early or Late time windows (p’s > 0.1). When ROI data were averaged across tasks and time windows, the right hemisphere showed no difference between groups, whereas the left hemisphere showed a trend for reduced MMN activity in FEP (p = 0.069). Post-hoc comparisons of the six left hemisphere ROIs revealed that all regions but Brodmann’s Area 43 showed significant reduction in FEP (p’s < 0.05).DiscussionThese findings support previous literature that indicate relatively preserved EEG scalp measures of MMN in FEP. However, the MEG source data indicate a deficit in the left hemisphere auditory cortex of FEP. This left hemisphere reduction was observed in 5 out of 6 source regions and at both time windows. This suggests broad left hemisphere auditory cortex pathophysiology early in disease course to which EEG may be relatively less sensitive by comparison with MEG. In conclusion, FEP may be associated with a selective left hemisphere MMN deficit in auditory regions on the superior temporal plane, but not the opercular cortex (i.e. Brodmann’s Area 43).

Focal Hemodynamic Responses in the Stimulated Hemisphere During High-Definition Transcranial Direct Current Stimulation

High-definition transcranial direct current stimulation (HD-tDCS) using a 4 × 1 electrode montage has been previously shown using modeling and physiological studies to constrain the electric field within the spatial extent of the electrodes. The aim of this proof-of-concept study was to determine if functional near-infrared spectroscopy (fNIRS) neuroimaging can be used to determine a hemodynamic correlate of this 4 × 1 HD-tDCS electric field on the brain. In a three session cross-over study design, 13 healthy males received one sham (2 mA, 30 sec) and two real (HD-tDCS-1 and HD-tDCS-2, 2 mA, 10 min) anodal HD-tDCS targeting the left M1 via a 4 × 1 electrode montage (anode on C3 and 4 return electrodes 3.5 cm from anode). The two real HD-tDCS sessions afforded a within-subject replication of the findings. fNIRS was used to measure changes in brain hemodynamics (oxygenated hemoglobin integral-O2 Hbint ) during each 10 min session from two regions of interest (ROIs) in the stimulated left hemisphere that corresponded to "within" (Lin ) and "outside" (Lout ) the spatial extent of the 4 × 1 electrode montage, and two corresponding ROIs (Rin and Rout ) in the right hemisphere. The ANOVA showed that both real anodal HD-tDCS compared to sham induced a significantly greater O2 Hbint in the Lin than Lout ROIs of the stimulated left hemisphere; while there were no significant differences between the real and sham sessions for the right hemisphere ROIs. Intra-class correlation coefficients showed "fair-to-good" reproducibility for the left stimulated hemisphere ROIs. The greater O2 Hbint "within" than "outside" the spatial extent of the 4 × 1 electrode montage represents a hemodynamic correlate of the electrical field distribution, and thus provides a prospective reliable method to determine the dose of stimulation that is necessary to optimize HD-tDCS parameters in various applications.

Global and Targeted Pathway Impact of Gliomas on White Matter Integrity Based on Lobar Localization.

Primary brain tumors comprise 28% of all tumors and 80% of malignant tumors. Pathophysiology of high-grade gliomas includes significant distortion of white matter architecture, necrosis, the breakdown of the blood brain barrier, and increased intracranial pressure. Diffusion tensor imaging (DTI), a diffusion weighted imaging technique, can be used to assess white matter architecture. Use of DTI as a non-invasive pathophysiological tool to analyze glioma impact on white matter microstructure has yet to be fully explored.Preliminary assessment of DTI tractography was done as a measure of intracranial tumor impact on white matter architecture. Specifically, we addressed three questions: 1) whether glioma differentially affects local white matter structure compared to metastasis, 2) whether glioma affects tract integrity of major white matter bundles, 3) whether glioma lobe localization affects tract integrity of different white matter bundles.In this study, we retrospectively investigated preoperative DTI scans from 24 patients undergoing tumor resection. Fiber tractography was estimated using a deterministic fiber tracking algorithm in DSI (diffusion spectrum imaging) Studio. The automatic anatomical labeling (AAL) atlas was used to define the left and right (L/R) hemisphere regions of interest (ROI). In addition, the John Hopkins University (JHU) White Matter Atlas was used to auto-segment major white matter bundle ROIs. For all tracts derived from ROI seed targets, we computed the following parameters: tract number, tract length, fractional anisotropy (FA), axial diffusivity (AD), mean diffusivity (MD), and radial diffusivity (RD).The DTI tractography analysis revealed that white matter integrity in the hemisphere ipsilateral to intracranial tumor was significantly compromised compared to the control contralateral hemisphere. No differences were observed between high vs low-grade gliomas, however, gliomas induced significantly greater white matter degradation than metastases. In addition, targeted analysis of major white matter bundles important for sensory/motor function (i.e., corticospinal tract and superior longitudinal fasciculus) revealed tract-parameter specific susceptibility due to the presence of the tumor. Finally, major tract bundles were differentially affected based on lobar localization of the glioma.These DTI-based tractographic analyses complement findings from gross histopathological examination of glioma impact on neural tissue. Global and focal white matter architecture, ipsilateral to glioma, shows higher rates of degradation or edema – based on DTI tractographic metrics – in comparison to normal brain or metastases. Gliomas, which arise in the parietal lobe, also have a higher negative impact (potentially due to increased edema) on white matter integrity of the superior longitudinal fasciculus(SLF) than those which arise in the frontal lobe. Future studies will focus on using preoperative and postoperative tractography to predict functional deficits following resective surgery.

Alterations of functional connectivities from early to middle adulthood: Clues from multivariate pattern analysis of resting-state fMRI data

In contrast to extended research interests in the maturation and aging of human brain, alterations of brain structure and function from early to middle adulthood have been much less studied. The aim of the present study was to investigate the extent and pattern of the alterations of functional interactions between brain regions from early to middle adulthood. We carried out the study by multivariate pattern analysis of resting-state fMRI (RS-fMRI) data of 63 adults aged 18 to 45years. Specifically, using elastic net, we performed brain age estimation and age-group classification (young adults aged 18–28years vs. middle-aged adults aged 35–45years) based on the resting-state functional connectivities (RSFCs) between 160 regions of interest (ROIs) evaluated on the RS-fMRI data of each subject. The results indicate that the estimated brain ages were significantly correlated with the chronological age (R=0.78, MAE=4.81), and a classification rate of 94.44% and area under the receiver operating characteristic curve (AUC) of 0.99 were obtained when classifying the young and middle-aged adults. These results provide strong evidence that functional interactions between brain regions undergo notable alterations from early to middle adulthood. By analyzing the RSFCs that contribute to brain age estimation/age-group classification, we found that a majority of the RSFCs were inter-network, and we speculate that inter-network RSFCs might mature late but age early as compared to intra-network ones. In addition, the strengthening/weakening of the RSFCs associated with the left/right hemispheric ROIs, the weakening of cortico-cerebellar RSFCs and the strengthening of the RSFCs between the default mode network and other networks contributed much to both brain age estimation and age-group classification. All these alterations might reflect that aging of brain function is already in progress in middle adulthood. Overall, the present study indicated that the RSFCs undergo notable alterations from early to middle adulthood and highlighted the necessity of careful considerations of possible influences of these alterations in related studies.

Auditory middle latency responses differ in right- and left-handed subjects: an evaluation through topographic brain mapping.

To investigate the association of handedness with auditory middle latency responses (AMLRs) using topographic brain mapping by comparing amplitudes and latencies in frontocentral and hemispheric regions of interest (ROIs). The study included 44 healthy subjects with normal hearing (22 left handed and 22 right handed). AMLRs were recorded from 29 scalp electrodes in response to binaural 4-kHz tone bursts. Frontocentral ROI comparisons revealed that Pa and Pb amplitudes were significantly larger in the left-handed than the right-handed group. Topographic brain maps showed different distributions in AMLR components between the two groups. In hemispheric comparisons, Pa amplitude differed significantly across groups. A left-hemisphere emphasis of Pa was found in the right-handed group but not in the left-handed group. This study provides evidence that handedness is associated with AMLR components in frontocentral and hemispheric ROI. Handedness should be considered an essential factor in the clinical or experimental use of AMLRs.

Sustained attention is associated with right superior longitudinal fasciculus and superior parietal white matter microstructure in children

Sustained attention develops during childhood and has been linked to the right fronto-parietal cortices in functional imaging studies; however, less is known about its relation to white matter (WM) characteristics. Here we investigated whether the microstructure of the WM underlying and connecting the right fronto-parietal cortices was associated with sustained attention performance in a group of 76 typically developing children aged 7-13 years. Sustained attention was assessed using a rapid visual information processing paradigm. The two behavioral measures of interest were the sensitivity index d' and the coefficient of variation in reaction times (RTCV ). Diffusion-weighted imaging was performed. Mean fractional anisotropy (FA) was extracted from the WM underlying right dorsolateral prefrontal (DLPFC) and parietal cortex (PC), and the right superior longitudinal fasciculus (SLF), as well as equivalent anatomical regions-of-interest (ROIs) in the left hemisphere and mean global WM FA. When analyzed collectively, right hemisphere ROIs FA was significantly associated with d' independently of age. Follow-up analyses revealed that only FA of right SLF and the superior part of the right PC contributed significantly to this association. RTCV was significantly associated with right superior PC FA, but not with right SLF FA. Observed associations remained significant after controlling for FA of equivalent left hemisphere ROIs or global mean FA. In conclusion, better sustained attention performance was associated with higher FA of WM in regions connecting right frontal and parietal cortices. Further studies are needed to clarify to which extent these associations are driven by maturational processes, stable characteristics and/or experience.

Relative utility for hemispheric lateralization of different clinical fMRI activation tasks within a comprehensive language paradigm battery in brain tumor patients as assessed by both threshold-dependent and threshold-independent analysis methods

The aim of this study was to compare the relative effectiveness of 6 different commonly used language fMRI activation paradigms, including receptive and expressive, as well as semantic and phonological tasks, for hemispheric lateralization in brain tumor patients utilizing both threshold-dependent and threshold-independent approaches. We studied 46 right-handed patients with primary intra-axial brain tumors with BOLD fMRI on a 3-T MRI system. A linear fit of the laterality indices (LIs) as a function of the t-value (which varied from 2.0 to 6.5) was calculated and the slope ( M) taken as measure of LI variability in the threshold-dependent LI approach; for the threshold-independent approach, the LIs were determined by comparing the integrated T-score weighted distributions of all positively task-correlated voxels of the left and the right hemispheric regions of interest. We demonstrated that silent word generation (SWG) and rhyming (R) were the two expressive tasks that provided the best hemispheric language lateralization in this group, based on concordant threshold-dependent and threshold-independent analyses. Furthermore, R (mean LI value = 61.91, M = 7.9 ± 1.5) had a higher mean LI value and was less threshold-dependent than SWG (mean LI = 52.97, M = 11.40 ± 0.64) for LI determination. SWG and R were able to provide effective language lateralization even in the subgroup of patients with lesions located in the left hemisphere and in the frontal or parietal lobes. The receptive language paradigms examined in this study (passive listening [PL], listening comprehension [LC], and reading comprehension [RC]) were less effective than SWG and R for language lateralization.

PRESURGICAL EVALUATION OF LANGUAGE USING FUNCTIONAL MAGNETIC RESONANCE IMAGING IN BRAIN TUMOR PATIENTS WITH PREVIOUS SURGERY

Functional magnetic resonance imaging (fMRI) is used to assess language laterality in preoperative brain tumor patients. In postsurgical patients, susceptibility artifacts can potentially alter ipsilateral fMRI activation volumes and the assessment of language laterality. The purpose of this study was to investigate the ability of fMRI to correctly measure language dominance in brain tumor patients with previous surgery because this patient cohort is vulnerable to type II statistical errors and subsequent misjudgment of laterality. Twenty-six right-handed patients with left-hemisphere gliomas (16 with and 10 without previous surgery) underwent preoperative language fMRI. Language laterality was measured using hemispheric and Broca's area regions of interest (ROIs). Hemisphere dominance, as established by laterality measurements, was compared with that determined by intraoperative electrocorticography and behavioral assessments. Localization of primary language cortices was achieved in 24 of 26 patients studied. The hemisphere dominance evaluated by fMRI was verified by intraoperative corticography in only 14 patients (10 with and 4 without previous surgery), and only 12 of them had complete neuropsychological testing. Complete concordance of the laterality with intraoperative electrocorticography and behavioral assessments was found in patients without previous surgery. In patients with previous surgery, concordance was 75% using Broca's area ROI and 88% using hemispheric ROI, notwithstanding susceptibility artifacts. Differences in laterality between pre- and postsurgical patients, based on either hemispheric (P = 0.81) or Broca's area (P = 0.19) ROI measurements were not statistically significant. However, hemispheric ROI analyses were found to be less affected by postsurgical artifacts and may be more suitable for establishing hemisphere dominance. fMRI mapping of eloquent language cortices in brain tumor patients after surgery is feasible and can serve as a useful baseline evaluation for preoperative neurosurgical planning. However, findings should be interpreted with caution in the presence of postsurgical artifacts.

Spatial-Temporal Current Source Correlations and Cortical Connectivity

The purpose of this study was to explore spatial-temporal correlations between 3-dimensional current density estimates using Low Resolution Electromagnetic Tomography (LORETA). The electroencephalogram (EEG) was recorded from 19 scalp locations from 97 subjects. LORETA current density was computed for 2,394 gray matter pixels. The gray matter pixels were grouped into 33 left hemisphere and 33 right hemisphere regions of interest (ROIs) based on groupings of Brodmann areas. The average source current density in a given region of interest (ROI) was computed for each 2 second epoch of EEG and then a Pearson product correlation coefficient was computed over the time series of successive 2 second epochs of current density between all pairwise combinations of ROIs during the resting eyes-closed EEG session. Rhythmic changes in source correlation as a function of distance were present in all regions of interest. Also, maximum correlations at certain frequencies were present independent of distance. The occipital regions exhibited the highest short distance correlations and the frontal regions exhibited the highest long distance correlations. In general, the right hemisphere exhibited higher intra-hemispheric source correlations than the left hemisphere especially in the temporal, parietal and occipital cortex. The strongest left vs. right hemisphere differences were in the alpha frequency band (8-12 Hz) and in the gamma frequency band (37-40 Hz). The pattern of spatial frequencies in different cortical lobules is consistent with differences in neural packing density and the operation of 'U' shaped fiber systems. The general conclusions were: 1--the higher the packing density then the greater the intra-cortical connection contribution to LORETA source correlations, 2--spatial frequencies are primarily due to intra-cortical 'U' shaped fiber connections and long distance fiber connections, 3--posterior and temporal cortical intra-hemispheric coupling is generally stronger in the right hemisphere than in the left hemisphere.

Cerebral perfusion computerized tomography: influence of reference vessels, regions of interest and interobserver variability

There are still no standardized guidelines for perfusion computerized tomography (PCT) analysis. A total of 61 PCT studies were analyzed using either the anterior cerebral artery (ACA) or the middle cerebral artery (MCA) as the arterial reference, and the superior sagittal sinus (SSS) or the vein of Galen (VG) as the venous reference. The sizes of regions of interest (ROI) were investigated comparing PCT results obtained using a hemispheric ROI combined with vascular pixel elimination with those obtained using five smaller ROIs located over the cortex and basal ganglia. In addition, interobserver variations were explored using a standardized protocol. MCA-based measurements of cerebral blood flow (CBF) and blood volume (CBV) were in accordance with those obtained with the ACA except in 16 patients with ischemic stroke, in whom CBF was overestimated by the ipsilateral MCA. Venous maximal intensity was significantly lower with the VG when compared with the SSS, resulting in overestimation of CBF and CBV. However, in 13.3% of patients the VG ROI yielded higher maximal intensities than the SSS ROI. There was no difference in PCT results between hemispheric ROI and averaged separate ROI when vascular pixel elimination was used. Finally, interobserver variations were as high as 11% for CBF and 12% for CBV. The present results suggest that pathological rather than anatomical considerations should dictate the choice of the arterial ROI. For venous ROI, although SSS seems to be adequate in most instances, deep cerebral veins may occasionally generate higher maximal intensities and should therefore be selected. Importantly, significant user-dependency should be taken into account.

Characterization of the Effects of Adenosine Receptor Agonists on Cerebral Blood Flow in Uninjured and Traumatically Injured Rat Brain using Continuous Arterial Spin-Labeled Magnetic Resonance Imaging

Hypoperfusion after traumatic brain injury may exacerbate damage. Adenosine, a vasodilator, regulates cerebral blood flow (CBF). Treatment with adenosine receptor agonists has shown benefit in experimental CNS trauma; however, their effects on CBF after injury remain undefined. We used magnetic resonance imaging to assess CBF in uninjured rats both early and at 24 h after intrahippocampal administration of either the nonselective adenosine receptor agonist 2-chloroadenosine (2-CA, 12 nmol) or the A(2A)-receptor agonist 2-p-(2-carboxyethyl)-phenethylamino-5'-N-ethylcarbox-amidoadenosine (CGS 21680, 6 nmol). We also assessed the effects of these agents on cerebral metabolic rate for glucose (CMRglu). We then assessed the effect of 2-CA on CBF at 3.5 to 5 h after controlled cortical impact (CCI). Injection of 2-CA into uninjured rat brain produced marked increases in CBF in ipsilateral hippocampus and cortex versus vehicle (P<0.05); CBF increases persisted even at 24 h. Measurement of hippocampal levels of 2-CA showed persistent increases to 24 h. CGS 21680 produced even more marked global increases in CBF than seen with 2-CA (2-6-fold versus vehicle, P<0.05 in 10/12 regions of interest (ROIs)). Neither agonist altered CMRglu versus vehicle. After CCI, 2-CA increased CBF in ipsilateral hippocampal and hemispheric ROIs (P<0.05 versus vehicle), but the response was attenuated at severe injury levels. We report marked increases in CBF after injection of adenosine receptor agonists into uninjured rat brain despite unaltered CMRglu. 2-Chloroadenosine produced enduring increases in CBF in uninjured brain and attenuated posttraumatic hypoperfusion. Future studies of adenosine-related therapies in CNS injury should address the role of CBF.

Language lateralization in left-handed and ambidextrous people: fMRI data.

It is generally accepted that most people have left-hemispheric language dominance, though the actual incidence of atypical language distribution in non-right-handed subjects has not been extensively studied. The authors examined language distribution in these subjects and evaluated the relationships between personal handedness, family history of sinistrality, and a language laterality index (LI) measured with fMRI. The authors used whole-brain fMRI to examine 50 healthy, non-right-handed subjects (Edinburgh Handedness Inventory quotient between -100 and 52) while they performed language activation and nonlinguistic control tasks. Counts of active voxels (p < 0.001) were computed in 22 regions of interest (ROI) covering both hemispheres and the cerebellum. LI were calculated for each ROI and each entire hemisphere using the formula [L - R]/[L + R]. Activation was predominantly right hemispheric in 8% (4/50), symmetric in 14% (7/50), and predominantly left hemispheric in 78% (39/50) of the subjects. Lateralization patterns were similar for all hemispheric ROI. Associations were observed between personal handedness and LI (r = 0.28, p = 0.046), family history of sinistrality and LI (p = 0.031), and age and LI (r = -0.49, p < 0.001). The incidence of atypical language lateralization in normal left-handed and ambidextrous subjects is higher than in normal right-handed subjects (22% vs 4-6%). These whole-brain results confirm previous findings in a left-handed cohort studied with fMRI of the lateral frontal lobe. Associations observed between personal handedness and LI and family history of handedness and LI may indicate a common genetic factor underlying the inheritance of handedness and language lateralization.

Functional Brain Imaging in Apraxia

An extensive literature describes structural lesions in apraxia, but few studies have used functional neuroimaging. We used positron emission tomography (PET) to characterize relative cerebral glucose metabolism in a 65-year-old, right-handed woman with progressive decline in ability to manipulate objects, write, and articulate speech. To characterize functional brain organization in apraxia. The patient underwent a neurological examination, neuropsychological testing, magnetic resonance imaging, and fludeoxyglucose F 18 PET. The patient's magnetic resonance image was coregistered to her PET image, which was compared with the PET images of 7 right-handed, healthy controls. Hemispheric regions of interest were normalized by calcrine cortex. Except for apraxia and mild grip weakness, results of the neurological examination were normal. There was ideomotor apraxia of both hands (command, imitation, and object) and buccofacial apraxia. The patient could recognize meaningful gestures performed by the examiner and discriminate between his accurate and awkward pantomime. The magnetic resonance image showed moderate generalized atrophy and mild ischemic changes. Positron emission tomographic scans showed abnormal fludeoxyglucose F 18 uptake in the posterior frontal, supplementary motor, and parietal regions, the left affected more than the right. Focal metabolic deficit was present in the angular gyrus, an area hypothesized to store conceptual knowledge of skilled movement. Greater parietal than frontal physiological dysfunction and preserved gesture recognition are not consistent with the theory that knowledge of limb praxis is stored in the dominant parietal cortex. Gesture comprehension may be more diffusely distributed.

Single photon emission computed tomography in dementia: relationship of perfusion to cognitive deficits.

Sixteen patients with dementia (nine with Alzheimer's disease and seven with multi-infarct dementia) were studied with xenon-133 and hexamethyl-propyleneamine-oxime single photon emission computed tomography (SPECT). Quantification of cerebral blood flow was determined in 16 hemispheric regions of interest. Neuropsychological deficits were assessed with the Mini-Mental State Examination and the Neurobehavior Cognitive Status Examination. Alzheimer's disease patients had symmetric reduction of parietal lobe perfusion; multi-infarct dementia patients had multifocal perfusion deficits. Correlations were demonstrated between cerebral blood flow in the posterior brain regions and performance on tests of language, memory, attention, figure copying, judgment, and similarities. Alzheimer's disease patients exhibited more language impairment than multi-infarct dementia patients. SPECT promises to provide diagnostic information and data relevant to interpretation of neuropsychological deficits.