Positron Emission Tomography Activation Studies Research Articles

Visualization of the auditory pathway in rats with 18F-FDG PET activation studies based on different auditory stimuli and reference conditions including cochlea ablation.

Activation studies with positron emission tomography (PET) in auditory implant users explained some of the mechanisms underlying the variability of achieved speech comprehension. Since future developments of auditory implants will include studies in rodents, we aimed to inversely translate functional PET imaging to rats. In normal hearing rats, activity in auditory and non-auditory regions was studied using 18F-fluorodeoxyglucose (18F-FDG) PET with 3 different acoustic conditions: sound attenuated laboratory background, continuous white noise and rippled noise. Additionally, bilateral cochlea ablated animals were scanned. 3D image data were transferred into a stereotaxic standard space and evaluated using volume of interest (VOI) analyses and statistical parametric mapping (SPM). In normal hearing rats alongside the auditory pathway consistent activations of the nucleus cochlearis (NC), olivary complex (OC) and inferior colliculus (IC) were seen comparing stimuli with background. In this respect, no increased activation could be detected in the auditory cortex (AC), which even showed deactivation with white noise stimulation. Nevertheless, higher activity in the AC in normal hearing rats was observed for all 3 auditory conditions against the cochlea ablated status. Vice versa, in ablated status activity in the olfactory nucleus (ON) was higher compared to all auditory conditions in normal hearing rats. Our results indicate that activations can be demonstrated in normal hearing animals based on 18F-FDG PET in nuclei along the central auditory pathway with different types of noise stimuli. However, in the AC missing activation with respect to the background advises the need for more rigorous background noise attenuation for non-invasive reference conditions. Finally, our data suggest cross-modal activation of the olfactory system following cochlea ablation–underlining, that 18F-FDG PET appears to be well suited to study plasticity in rat models for cochlear implantation.

Imaging effects related to language improvements by rTMS.

The functional deficit after a focal brain lesion is determined by the localization and the extent of the tissue damage. Since destroyed tissue usually cannot be replaced in the adult human brain, improvement or recovery of neurological deficits can be achieved only by reactivation of functionally disturbed but morphologically preserved areas or by recruitment of alternative pathways within the functional network. The visualization of disturbed interaction in functional networks and of their reorganization in the recovery after focal brain damage is the domain of functional imaging modalities such as positron emission tomography (PET). Longitudinal assessments at rest and during activation tasks during the early and later periods following a stroke can demonstrate recruitment and compensatory mechanisms in the functional network responsible for complete or partial recovery of disturbed functions. Imaging studies have shown that improvements after focal cortical injury are represented over larger cortical territories. It has also been shown that the unaffected hemisphere in some instances actually inhibits the recovery of ipsilateral functional networks and this effect of transcallosal inhibition can be reduced by non-invasive brain stimutation. Non-invasive brain stimulation (NIBS) can modulate the excitability and activity of targeted cortical regions and thereby alter the interaction within pathologically affected functional networks; this kind of intervention might promote the adaptive cortical reorganization of functional networks after stroke. In poststroke aphasia several studies attempted to restore perilesional neuronal activity in the injured left inferior frontal gyrus by applying excitatory high frequency repetitive transcranial magnetic stimulation (rTMS) or intermittent theta burst stimulation (iTBS) or anodal transcranial direct current stimulation (tDCS), but most NIBS studies in poststroke aphasia employed inhibitory low frequency rTMS for stimulation of the contralesional pars triangularis of the right inferior frontal gyrus (BA 45) in order to reduce right hemisphere hyperactivity and transcallosal inhibition on the left Broca's area. While most studies reported single cases or small case series with chronic poststroke aphasia without any control condition, only a few controlled studies including sham stimulation were performed in chronic stage after stroke. In one controlled randomized study changes in PET activation pattern in the subacute course were related to the clinical improvement. In this "proof-of-principle" study the shift of the activation pattern to the dominant hemisphere induced by inhibitory rTMS over the right inferior frontal gyrus could be demonstrated in the PET activation studies and correlated to improved performance in aphasia tests. NIBS might be a treatment strategy which could improve the effect of other rehabilitative efforts.

Central executive function in mild cognitive impairment: A PET activation study

Using positron emission tomography (PET), we explored the neural correlates of an executive function, dual tasking, in patients with amnestic mild cognitive impairment (aMCI) and in elderly controls. The experiment employed simple auditory and visual tasks that were presented both in isolation and simultaneously to create a task condition requiring enhanced attentional control. Behaviorally, both groups performed well, albeit the patients made more errors on the visual task. The PET analysis focused at prefrontal regions where group differences in task-related activation patterns were expected. During dual task performance, the patients showed attenuated activity in the left inferior frontal region when compared to the controls. This suggests abnormalities in the neural processes underlying attentional control in aMCI.

Age‐related changes in the cerebral substrates of cognitive procedural learning

Cognitive procedural learning occurs in three qualitatively different phases (cognitive, associative, and autonomous). At the beginning of this process, numerous cognitive functions are involved, subtended by distinct brain structures such as the prefrontal and parietal cortex and the cerebellum. As the learning progresses, these cognitive components are gradually replaced by psychomotor abilities, reflected by the increasing involvement of the cerebellum, thalamus, and occipital regions. In elderly subjects, although cognitive studies have revealed a learning effect, performance levels differ during the acquisition of a procedure. The effects of age on the learning of a cognitive procedure have not yet been examined using functional imaging. The aim of this study was therefore to characterize the cerebral substrates involved in the learning of a cognitive procedure, comparing a group of older subjects with young controls. For this purpose, we performed a positron emission tomography activation study using the Tower of Toronto task. A direct comparison of the two groups revealed the involvement of a similar network of brain regions at the beginning of learning (cognitive phase). However, the engagement of frontal and cingulate regions persisted in the older group as learning continued, whereas it ceased in the younger controls. We assume that this additional activation in the older group during the associative and autonomous phases reflected compensatory processes and the fact that some older subjects failed to fully automate the procedure.

Mechanisms of increased airway sensitivity to occupational chemicals and odors

Airway symptoms induced by chemicals and odors are common problems that are also reported after contact with substances normally regarded as nontoxic. This article reviews current findings and opinions regarding mechanisms of increased airway sensitivity to occupational chemicals and odors. Individuals exposed to organic solvents during work had more nasal irritation and lower threshold to pyridine odor compared with a nonexposed control group. Six percentage of a general population in Sweden had pronounced airway chemical sensitivity and augmented capsaicin cough sensitivity, known to reflect the sensory nerve reactivity of the airways. The cough sensitivity was associated with changed levels of nerve growth factor in nasal lavage and such patients had longstanding symptoms influencing their working capacity. Positron emission tomography activation studies with several different odorants showed in patients with odor-associated symptoms an odorant-related increase in activation of the anterior cingulate cortex and cuneus-precuneus in comparison with a control group. In subgroups of individuals with airway symptoms induced by chemicals and odors, there seems to be a sustainable physiological mechanism behind the reactions. An increased vulnerability to stress cannot be neglected as a confounding factor in some sensitive individuals.

Brain function during multi-trial learning in mild cognitive impairment: A PET activation study

We explored functional brain changes with positron emission tomography (PET) in mild cognitive impairment (MCI) patients and elderly normal controls by employing an episodic memory task that included two successive encoding trials of semantically related word-pairs and final retrieval. Both groups demonstrated significant learning across the two trials. The control group showed predominantly left frontal activity during encoding, and right frontal plus left temporal activity during retrieval. However, the MCI patients recruited partly different brain regions. They failed to activate right frontal and left temporal areas during retrieval, and failed to show any different activation for encoding on the first and second trials, whereas the controls activated a region of posterior cingulate. There was indication of compensatory increases in rCBF of the occipital cortex during incremental learning and the left frontal lobe during retrieval in the patients. These results suggest different episodic memory processing in the MCI group, and a possible over-reliance on semantic processing. Subtle functional changes occur in the pre-Alzheimer brain before there are marked structural or behavioural abnormalities.

Functional Neuroimaging Applications for Assessment and Rehabilitation Planning in Patients With Disorders of Consciousness

Giacino JT, Hirsch J, Schiff N, Laureys S. Functional neuroimaging applications for assessment and rehabilitation planning in patients with disorders of consciousness. Objective To describe the theoretic framework, design, and potential clinical applications of functional neuroimaging protocols in patients with disorders of consciousness. Data Sources Recent published literature and authors’ own work. Study Selection Studies using functional neuroimaging techniques to investigate cognitive processing in patients diagnosed with vegetative and minimally conscious state. Data Extraction Not applicable. Data Synthesis Positron-emission tomography activation studies suggest that the vegetative state represents a global disconnection syndrome in which higher order association cortices are functionally disconnected from primary cortical areas. In contrast, patterns of activation in functional magnetic resonance imaging studies of patients in the minimally conscious state show preservation of large-scale cortical networks associated with language and visual processing. Conclusions Novel applications of functional neuroimaging in patients with disorders of consciousness may aid in differential diagnosis, prognostic assessment and identification of pathophysiologic mechanisms. Improvements in patient characterization may, in turn, provide new opportunities for restoration of function through interventional neuromodulation.

Naming of newly learned objects: A PET activation study

The present study tracked the naming-related brain activity by positron emission tomography (PET) when successfully learned unfamiliar objects were named. Ten Finnish-speaking subjects participated in the study. Prior to the PET scan, each subject underwent a 4-day long training period in which 40 names of rare unfamiliar objects were taught. The stimulus categories were as follows: unfamiliar but real objects for which both the name and the definition were given during training, only the name was given, no information was given. In addition, familiar objects and visual noise patterns were used. The unfamiliar items mainly represented ancient domestic tools unknown to modern-day people. As semantic support did not affect the PET results, all trained items were pooled together. The trained objects vs. familiar objects contrast revealed rCBF increases in the left inferior frontal cortex (Broca's area), the left anterior temporal area, and the cerebellum. Likewise, the trained objects vs. unfamiliar objects (for which no information was given) contrast revealed more extensive left frontal (roughly Broca's area) and cerebellar rCBF increases, while anterior temporal activation was bilateral. Familiar objects, contrasted with both visual noise patterns and a rest condition, elicited activation increases in expected areas, i.e., bilateral occipital regions and the fusiform gyrus. Our results indicate that the naming of newly learned objects recruits more extensive brain areas than the naming of familiar items, namely a network that includes left-dominant frontotemporal areas and cerebellum. Its activity is tentatively related to enhanced lexical–semantic and lexical–phonological retrieval, as well as associative memory processes.

Cerebellar Involvement in Visual On-Line Adaptation of Vertical Stroke Size: A PET Activation Study

Introduction: Behavioral data suggest that visual feedback can be effectively used for on-line adjustment of letter size during open-loop automated handwriting (Mai et Marquart Exp Brain Res 1999; 128: 224–228). Objective: Our intent was to pinpoint the involvement of the cerebellum in visual on-line adaptation of letter size. Methods: In eight male right-handed subjects (age: 25–39 years), we used H2 15O positron emission tomography (PET) to measure regional cerebral blood flow (rCBF) during a handwriting task and a control condition (holding the pen). The written trace was recorded using a graphics tablet. Visual feedback of handwriting was continuously provided on a computer screen. In each trial, participants wrote four pairs of „l„ („ll ll ll ll“) every six seconds. Subjects were asked to match the letter size to the distance between two horizontal lines (˜ 9mm) using the feedback on the screen. The critical manipulation was an unpredictable change in the gain of vertical feedback during each trial. After the subject had written the first pair of „l“, the gain of vertical feedback was either reduced to 66% (1/3 of the trials), enlarged to 133% (1/3 of the trials) or remained the same (1/3 of the trials). Subjects were asked to maintain stroke size as specified by the horizontal lines. Kinematics of handwriting were analyzed using CS software (MedCom, Munich, Germany). The mean number of inversions in velocity (NIV) was calculated for each scan to quantify the degree of automation. Three scans per condition were acquired in each subject. PET data were analyzed with SPM99 (Wellcome Dept. of Neuroscience, ION, UCL, UK). Using a general linear model, the NIV were treated as a regressor to model the changes in rCBF associated with the mean NIV per scan (p<0.001, uncorrected). Results: Regression analysis revealed a positive linear relationship between the rCBF in several cerebellar clusters and the degree of automation during handwriting (i.e., as indexed by the NIV). These cerebellar areas were located bilaterally in the medial and paramedian aspects of the superior cerebellum. Conclusion: Our findings demonstrate that a high degree of open-loop performance is associated with an increased cerebellar activity during a task requiring rapid integration of visual feedback. This activity pattern points to a significant role of the cerebellum in on-line adjustments of movement amplitude during skilled hand movements.

Schizophrenia Revealed: From Neurons to Social Interactions

Back to table of contents Previous article Next article Book ReviewsFull AccessSchizophrenia Revealed: From Neurons to Social InteractionsAnn L. Hackman, M.D.Ann L. HackmanSearch for more papers by this author, M.D.Published Online:1 Feb 2003https://doi.org/10.1176/appi.ps.54.2.261-aAboutSectionsView EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail Schizophrenia Revealed begins with the premise that in many ways schizophrenia has long been viewed as a mystery. However, over the past decade advances in research and changing perspectives on schizophrenia have greatly improved understanding of this illness. In this book, Michael Foster Green, Ph.D., describes major recent developments in schizophrenia research.The text is divided into seven chapters. The first considers the features of schizophrenia from early views of the disorder in the works of Bleuler and Kraepelin to clinical symptoms, including positive, negative, and disorganized symptoms to DSM-IV diagnosis. The second chapter reviews the literature on the development of schizophrenia, and the third addresses genetics. Dr. Green considers risk factors and the concept of risk versus onset of illness, reviews population studies, examines markers of abnormal development, explains microscopic studies of the brain and the concept of cell migration in the development of neural connections, and addresses family studies, twin studies, and adoption studies as well as molecular genetics.Chapter 4 is titled "Neurocognitive Deficits" and describes research in schizophrenia involving problems in perception, attention, memory, problem solving, and some aspects of language as well as the tests used to evaluate these areas of functioning. The text flows easily into the next chapter and discussion of neuroimaging in schizophrenia. Early efforts at neuroimaging are described, followed by findings of positron emission tomography (PET) scanning, PET activation studies, magnetic resonance imaging, magnetic resonance spectroscopy, and diffusion tensor imaging; the section concludes with a discussion of disrupted brain regions versus neural circuits.The last two chapters address interventions and outcomes in schizophrenia. Among the interventions discussed are historical approaches such as wet packs; medications, including first-generation and new-generation antipsychotics; interventions for neurocognitive deficits; family interventions, such as family psychoeducation; and interventions for functional outcome, including assertive community treatment and social skills training. The text considers domains of outcome and personal determinants of functional outcome.Dr. Green has done a remarkable job in writing Schizophrenia Revealed. The book is designed to work at many levels and succeeds at being everything from an appropriate introductory text for the relatively sophisticated lay reader with an interest in schizophrenia to a good review of current research for a clinician psychiatrist working in the community. Like the best teachers, Dr. Green has a knack for explaining complex concepts in a fashion that makes them accessible. Furthermore, adept use of analogies, case material, references to popular films, and quotations from the likes of Mark Twain and Oscar Wilde make Schizophrenia Revealed a fascinating and compelling read.Dr. Hackman is medical director of programs of assertive community treatment at the University of Maryland Medical System in Baltimore.by Michael Foster Green, Ph.D.; New York, W.W. Norton and Company, 2001, 206 pages, $32 FiguresReferencesCited byDetailsCited ByNone Volume 54Issue 2 February 2003Pages 261-a-262 Metrics History Published online 1 February 2003 Published in print 1 February 2003

Detecting Residual Cognitive Function in Persistent Vegetative State

Despite converging agreement about the definition of persistent vegetative state, recent reports have raised concerns about the accuracy of diagnosis in some patients, and the extent to which, in a selection of cases, residual cognitive functions may remain undetected. Objective assessment of residual cognitive function can be extremely difficult as motor responses may be minimal, inconsistent, and difficult to document in many patients, or may be undetectable in others because no cognitive output is possible. Here we describe strategies for using H 2 15 O positron emission tomography activation studies to study covert cognitive processing in patients with a clinical diagnosis of persistent vegetative state. Three cases are described in detail. Of these, two exhibited clear and predicted regional cerebral blood flow responses during well-documented activation paradigms (face recognition and speech perception) which have been shown to produce specific, robust and reproducible activation patterns in normal volunteers. Some months after scanning, both patients made a significant recovery. In a third case, blood flow data were acquired during a speech perception task, although methodological difficulties precluded any systematic interpretation of the results. In spite of the multiple logistic and procedural problems involved, these results have major clinical and scientific implications and provide a strong basis for the systematic study of possible residual cognitive function in patients diagnosed as being in a persistent vegetative state.

Effects of incidental and intentional feature binding on recognition: a behavioural and PET activation study

Using Positron Emission Tomography (PET), we investigated cerebral regions associated with the episodic recognition of words alone and words bound to contextual colours. Two modes of colour encoding were tested: incidental and intentional word-to-colour binding. Word-only recognition was associated with brain activation in a lexico-semantic left middle temporal region and in the cerebellum following an incidental colour encoding, and with brain activation in the left posterior middle frontal gyrus, right anterior cingulate and right inferior frontal gyrus following an intentional encoding. Recognition of bound features was associated with activation in left prefrontal and superior parietal regions following an incidental colour encoding, and with preferential right prefrontal cortex activation following an intentional colour encoding. Our results are in line with the hypothesis of a parietal involvement in context processing, and prefrontal areas in monitoring retrieval processes. Our results also support the hypothesis of a ‘cortical asymmetry for reflective activity’ (CARA).

Learning face-name associations and the effect of age and performance: a PET activation study

Learning face-name associations is a complex task to be mastered in every day life that approaches the limits of cognitive capacity in most normal humans. We studied brain activation during face-name learning using positron emission tomography (PET) in 11 normal volunteers. The most intense activation was seen in occipital association cortex (BA 18) bilaterally, also involving lingual and fusiform gyrus (BA 37). In the left hemisphere additional activation were located in inferior temporal gyrus, the inferior part of pre- and postcentral gyrus, and orbitofrontal cortex (BA 11), whereas in the right hemisphere only a region in the precuneus (BA 19) was activated additionally. There was considerable interindividual variation of encoding success, which was significantly related to activation of BA 18 bilaterally. Subject ages covered a range of 26–72 years, but — in contrast to the effect of encoding success — there was no significant age effect on activations. Task-independent habituation effects were seen in cerebellum and left middle temporal gyrus. These results indicate that the intensity of information processing in ventral occipital association cortex is most important for success of face-name encoding. Learning is further mediated by a predominantly left-hemispheric network including inferior temporal and orbitofrontal cortex.

A versatile, low-cost method for presenting visual stimuli during MRI.

A visual presentation system is described that is inexpensive, easily implemented, and adaptable to most laboratory and clinical settings. Performance evaluations demonstrated a field of view of 26 x 56 degrees, no radiofrequency interference, and high image quality. Although the system was designed for brain activation studies with functional magnetic resonance imaging (MRI), it can also be used for positron emission tomography activation studies and for presenting relaxation videos during clinical MRI.

Cortical motor and somatosensory representation: effect of cerebral lesions.

Changes in cortical representation in patients with cerebral lesions may alter the correlation between cortical anatomy and function. This is of potential clinical significance when the extent of cortical resection is based on surface anatomical landmarks. Fifty-one patients with supratentorial lesions were studied. Nineteen harbored noncentral lesions (no involvement of pre- or postcentral gyrus), whereas 32 had central lesions. Control studies consisted of stimulation of the hand contralateral to the unaffected hemisphere. Positron emission tomography activation studies were performed using the [15O]H2O tracer. Somatosensory stimulation of the hand or foot was performed using a mechanical vibrator. Motor activation consisted of hand clenching or foot tapping. The t-statistic volumes were generated from images showing the mean change in regional cerebral blood flow, and coregistered with a T1-weighted magnetic resonance image. At the threshold selected, exclusive contralateral primary sensorimotor cortex activation was elicited in 100% of the control studies. A different pattern of cortical activation was associated with central lesions in 35 (78%) of 45 patients, which occurred significantly more often than with noncentral lesions (eight [31%] of 26 patients). The most common difference in the pattern of activation with central lesions was activation of cortical regions outside the central area (including the supplementary sensorimotor area and the secondary somatosensory cortex). No sensorimotor activation was observed in gyri adjacent to the pre- or postcentral gyrus. Central lesions are more frequently associated with altered patterns in activation than lesions in noncentral locations. Characteristic patterns include activation of secondary sensorimotor areas. The absence of activation in gyri adjacent to the sensorimotor strip has clinical significance for the planning of resections in the central area.

Localization of somatosensory function by using positron emission tomography scanning: a comparison with intraoperative cortical stimulation

Object To investigate the utility of [15O]H2O positron emission tomography (PET) activation studies in the presurgical mapping of primary somatosensory cortex, the authors compared the magnitude and location of activation foci obtained using PET scanning with the results of intraoperative cortical stimulation (ICS). Methods The authors used PET scanning and vibrotactile stimulation (of the face, hand, or foot) to localize the primary somatosensory cortex before surgical resection of mass lesions or epileptogenic foci affecting the central area in 20 patients. With the aid of image-guided surgical systems, the locations of significant activation foci on PET scanning were compared with those of positive ICS performed at craniotomy after the patient had received a local anesthetic agent. In addition, the relationship between the magnitude and statistical significance of blood flow changes and the presence of positive ICS was examined. In 22 (95.6%) of 23 statistically significant (p &lt; 0.05) PET activation foci, spatially concordant sites on ICS were also observed. Intraoperative cortical stimulation was positive in 40% of the PET activation studies that did not result in statistically significant activation. In the patients showing these results, there was a clearly identifiable t-statistic peak that was spatially concordant with the site of positive ICS in the sensorimotor area. All PET activation foci with a t statistic greater than 4.75 were associated with spatially concordant sites of positive ICS. All PET activation foci with a t statistic less than 3.2 were associated with negative ICS. Conclusions Positron emission tomography is an accurate method for mapping the primary somatosensory cortex before surgery. The need for ICS, which requires local anesthesia, may be eliminated when PET foci with high (&gt; 4.75) or low (&lt; 3.20) t-statistic peaks are elicited by vibrotactile stimulation.

Localization of hand motor activation in Broca's pli de passage moyen.

The object of this study was to identify a reliable surface landmark for the hand motor area and to demonstrate that it corresponds to a specific structural component of the precentral gyrus. Positron emission tomography (PET) activation studies for hand motor function were reviewed in 12 patients in whom magnetic resonance imaging results were normal. Each patient performed a hand opening and closing task. Using a computer-assisted three-dimensional reconstruction of the surface of each hemisphere studied, the relationship of the hand motor area with cortical surface landmarks was evaluated. The region of hand motor activation can be reliably identified on the surface of the brain by assessing anatomical relationships to nearby structures. After identification of the central sulcus, the superior and middle frontal gyrus can be seen to arise from the precentral gyrus at a perpendicular angle. A bend or genu in the precentral gyrus is constantly seen between the superior and middle frontal gyrus, which points posteriorly (posteriorly convex). The location of hand motor function, identified using PET activation studies, is within the central sulcus at the apex of this posteriorly pointing genu. The apex of the genu of the precentral gyrus leads to a deep cortical fold connecting the pre- and postcentral gyri and elevating the floor of the central sulcus. This deep fold was described by Paul Broca as the pli de passage fronto-parietal moyen, and the precentral bank of the pli de passage represents the anatomical substratum of hand motor function. Observers blinded to the results of the activation studies were able to identify the hand motor area reliably after instruction in using these surface landmarks.

Butanol is superior to water for performing positron emission tomography activation studies.

[15(O)]Butanol has been shown to be superior to [15(O)]water for measuring cerebral blood flow with positron emission tomography. This work demonstrates that it is also superior for performing activation studies. Data were collected under three conditions: a visual confrontation animal-naming task, nonsense figure size discrimination, and a nonvisual darkroom control task. Time-activity curves (TAC) were obtained for regions known to be activated by the confrontation naming task to compare absolute uptake and the different kinetics of the two tracers. Also, t statistic maps were calculated from the data of 10 subjects for both tracers and compared for magnitude of change and size of activated regions. Peak uptake in the whole-brain TAC were similar for the two tracers. For all regions and conditions, the washout rate of [15(O)]butanol was 41% greater than that of [15(O)]water. At a threshold of 0, the [15(O)]water and [15(O)]butanol percent difference (nonnormalized) and t statistic (global normalization) images are nearly identical, indicating that the same property is being measured with both tracers. The [15(O)]butanol parametric images displayed at a threshold of /t/ = 5 look similar to the [15(O)]water parametric maps displayed at a threshold of /t/ = 4, which is consistent with the observation that t statistic values in [15(O)]butanol images are generally greater. The t statistic values were equal when the [15(O)]butanol parametric map was created from any subset of 6 subjects and the [15(O)]water parametric map was created from all 10 subjects. Fewer subjects need to be studied with [15(O)]butanol to reach the same statistical power as an [15(O)]water-based study.

Response from Paulesu and Mehler

As discussed by ourselves[1xRight on in sign language. Paulesu, E. and Mehler, J. Nature. 1998; 392: 233–234Crossref | PubMed | Scopus (17)See all References][1]and also by Hickok and colleagues in the preceding comment[2xWhat's right about the neural organization of sign language? A perspective on recent neuroimaging results. Hickok, G., Bellugi, U., and Klima, E. Trends Cognit. Sci. 1998; 2: 465–468Abstract | Full Text | Full Text PDF | PubMed | Scopus (33)See all References][2]and elsewhere[3xLanguage, modality and the brain. Bellugi, U., Poizner, H., and Klima, E. Trends Neurosci. 1989; 12: 380–388Abstract | Full Text PDF | PubMed | Scopus (79)See all References][3], we believe that the available evidence from fMRI and other studies points to a left hemispheric dominance for language, even in the case of sign language[4xThe neurobiology of sign language and its implications for the neural basis of language. Hickok, G., Bellugi, U., and Klima, E. Nature. 1996; 381: 699–702Crossref | PubMed | Scopus (97)See all References, 5xNeural correlates of thinking in sign language. McGuire, P. et al. NeuroReport. 1997; 8: 695–698Crossref | PubMedSee all References, 6xSign language aphasia during left-hemisphere Amytal injection. Damasio, A. et al. Nature. 1986; 322: 363–365Crossref | PubMed | Scopus (35)See all References]. However, while the left hemispheric activations seen in recent imaging data for sign language could be largely predicted from lesion data, we are still inclined to believe, in contrast to Hickok et al.[2xWhat's right about the neural organization of sign language? A perspective on recent neuroimaging results. Hickok, G., Bellugi, U., and Klima, E. Trends Cognit. Sci. 1998; 2: 465–468Abstract | Full Text | Full Text PDF | PubMed | Scopus (33)See all References][2], that the right hemispheric activations described by Neville et al.[7xCerebral organization for language in deaf and hearing subjects: biological constraints and effects of experience. Neville, H. et al. Proc. Natl. Acad. Sci. U. S. A. 1998; 95: 922–929Crossref | PubMed | Scopus (302)See all References][7]are not artefactual—even though a real surprise, given the expectation from patient data. The baseline for the sign-language comprehension task used by Neville et al. (observation of non-linguistic gestures made by a signer) was closely matched to the experimental task. Auditory-language comprehension tasks using a similarly close baseline, such as backwards speech, do not show such prominent activations in the right hemisphere[8xThe bilingual brain: proficiency and age of acquisition of the second language. Perani, D. et al. Brain. 1998; 121: 1841–1852Crossref | PubMed | Scopus (370)See all References][8].As we proposed in our commentary[1xRight on in sign language. Paulesu, E. and Mehler, J. Nature. 1998; 392: 233–234Crossref | PubMed | Scopus (17)See all References][1], reconciliation of the mismatch between functional imaging and lesion data will require further investigations on both sides. Even if our suggestion[1xRight on in sign language. Paulesu, E. and Mehler, J. Nature. 1998; 392: 233–234Crossref | PubMed | Scopus (17)See all References][1]turned out to be true—that the right hemispheric activations seen for sign language by Neville et al. could have been due to prosodic processing[9xDominant language functions of the right hemisphere? Prosody and emotional gesturing. Ross, E. and Mesulam, M. Arch. Neurol. 1979; 36: 144–148Crossref | PubMed | Scopus (381)See all References][9]—this would still be a challenge for our understanding of the biological causes of the regional brain distribution of linguistic competences in both hearing and congenitally deaf subjects. Left-sided `dominance', together with right-sided linguistic competence of the kind seen in hearing subjects[9xDominant language functions of the right hemisphere? Prosody and emotional gesturing. Ross, E. and Mesulam, M. Arch. Neurol. 1979; 36: 144–148Crossref | PubMed | Scopus (381)See all References, 10xThe role of the right hemisphere in the interpretation of figurative aspects of language: a positron emission tomography activation study. Bottini, G. et al. Brain. 1994; 117: 1231–1253Crossref | PubMed | Scopus (407)See all References], is a complex scenario that is not evaluated by the hypotheses usually discussed in neuro-linguistics and neither is it discussed by Hickok et al. in their present comment.

Neural basis of an inherited speech and language disorder.

Investigation of the three-generation KE family, half of whose members are affected by a pronounced verbal dyspraxia, has led to identification of their core deficit as one involving sequential articulation and orofacial praxis. A positron emission tomography activation study revealed functional abnormalities in both cortical and subcortical motor-related areas of the frontal lobe, while quantitative analyses of magnetic resonance imaging scans revealed structural abnormalities in several of these same areas, particularly the caudate nucleus, which was found to be abnormally small bilaterally. A recent linkage study [Fisher, S., Vargha-Khadem, F., Watkins, K. E., Monaco, A. P. & Pembry, M. E. (1998) Nat. Genet. 18, 168-170] localized the abnormal gene (SPCH1) to a 5. 6-centiMorgan interval in the chromosomal band 7q31. The genetic mutation or deletion in this region has resulted in the abnormal development of several brain areas that appear to be critical for both orofacial movements and sequential articulation, leading to marked disruption of speech and expressive language.