[Neuroimaging of subcortical circuits].
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Animals↗
Biomedical subjects
S Lehéricy
Publications and source records attributed to S Lehéricy.
[Functional magnetic resonance imaging in clinical practice].
In the last decade, functional MRI (fMRI) has become one of the most widely used functional imaging technique in neurosciences. However, its clinical applications remain limited. Despite methodological and practical issues, fMRI data has been validated by different techniques (magnetoencephalography, Wada test, electrical and magnetic stimulations, and surgical resections). In neurosurgical practice, fMRI can identify eloquent areas involved in motor and language functions, and may evaluate characteristics of postoperative neurological deficit including its occurrence, clinical presentation and duration. This may help to inform patients and to prepare postoperative care. fMRI may also identify epileptic foci. In neurological practice, fMRI may help to determine prognosis of recovery after stroke, appropriate medication, and rehabilitation. fMRI may help to identify patients at risk of developing Alzheimer disease. Finally, cerebrovascular reactivity imaging is an interesting approach that might provide new radiological insights of vascular function.
Brain↗
Disorganized somatotopy in the putamen of patients with focal hand dystonia.
OBJECTIVE: To explore the selectivity of neuronal somatotopic representation in the striatum of patients with unilateral task-specific dystonia of the right arm. MATERIALS AND METHODS: The authors used fMRI in 14 right-handed dystonic subjects to examine putaminal organization. Subjects performed flexion/extension of the right and left fingers and toes, and contraction of the lips. RESULTS: Compared to healthy volunteer subjects, dystonic subjects had altered somatotopic organization in the left putamen, contralateral to the affected hand. Disease severity correlated with underactivation and decreased distance between right hand and lip representations. In the right putamen, ipsilateral to the affected hand, the somatotopic organization was not altered but disease severity also correlated with reduced distances between limbs. CONCLUSION: In dystonia there may be a dedifferentiation of the normally segregated cortico-subcortical sensorimotor maps in the putamen, which may contribute to the loss of functional selectivity of muscle activity observed in these dystonic subjects.
Adult↗
Neural network involved in time perception: an fMRI study comparing long and short interval estimation.
In this study, long ( approximately 1,300 ms) and short duration ( approximately 450 ms) estimation trials in an event-related functional MRI (fMRI) study were contrasted in order to reveal the regions within a time estimation network yielding increased activation with the increase of the duration to be estimated. In accordance with numerous imaging studies, our results showed that the presupplementary motor area (preSMA), the anterior cingulate, the prefrontal and parietal cortices, and the basal ganglia were involved in the estimation trials whatever the duration to be estimated. Moreover, only a subset of the regions within this distributed cortical and subcortical network yielded increased activation with increasing time, namely, the preSMA, the anterior cingulate cortex, the right inferior frontal gyrus (homolog to Broca's area), the bilateral premotor cortex, and the right caudate nucleus. This suggests that these regions are directly involved in duration estimation. We propose that the caudate-preSMA circuit, the anterior cingulate, and the premotor-inferior frontal regions may support a clock mechanism, decision and response-related processes, and active maintenance of temporal information, respectively.
Adult↗
Specific cerebral networks for maintenance and response organization within working memory as evidenced by the 'double delay/double response' paradigm.
Most of the working memory (WM) tasks used in functional imaging studies are based on the principle of the delayed response in which both the storage and the response organization are present during the delay period. It is therefore difficult to isolate activation specific to the storage function from that specific to the organization of the response. To determine the specific neural networks associated with these two WM operations, we performed a functional MRI study in healthy subjects using a new paradigm, 'the double delay/double response' tasks. This paradigm isolates maintenance from response organization by dividing the delay into two separate parts, the first being dedicated to memory, while the second includes response organization. Activation within the dorsolateral prefrontal cortex (DLPFC) followed a relative hemispheric dissociation: activation related to maintenance was predominant in the right DLPFC but was only detected when the load exceeded three items. Activation related to response organization was predominant in the left DLPFC, regardless of whether this response was based on information held in WM ('memory guided') or was independent of WM ('visually-guided'). These results suggest that activation of the DLPFC, should be interpreted in terms of executive processing for both maintenance and response organization.
Adult↗
Role of the healthy hemisphere in recovery after resection of the supplementary motor area.
OBJECTIVE: To determine the compensatory mechanisms involved in the recovery of motor function following surgical lesions of the supplementary motor area (SMA) and their relation to the clinical characteristics of recovery. SUBJECTS AND METHODS: Twelve patients were referred for surgery of low-grade gliomas located in the SMA, and compared to eight healthy controls using fMRI before and after surgery during self-paced movements of both hands, successively. Magnitude and volume of activation within regions of interest (primary sensorimotor cortex, premotor cortex, SMA, preSMA, and parietal lobes) were compared and tested for correlation with anatomic characteristics of the tumor and resection, and clinical data. RESULTS: Tumor growth induced preoperative underactivity in the adjacent SMA and overactivity in the opposite SMA. Postoperative recovery was associated with recruitment of a premotor network located in the healthy hemisphere including the SMA and the lateral premotor cortex. Postoperative premotor recruitment in the healthy hemisphere increased with the percentage of resection of preoperative SMA activation. Shortened onset and duration of recovery was associated with increased preoperative changes in activation levels. CONCLUSIONS: These findings suggest a dysfunction of the SMA ipsilateral to the tumor, partially compensated by a recruitment of the contralesional SMA which correlated with shortened postoperative recovery. SMA resection was compensated by the recruitment of a medial and lateral premotor circuitry in the healthy hemisphere.
Adult↗
Postoperative speech disorder after medial frontal surgery: role of the supplementary motor area.
BACKGROUND: Patients undergoing surgical resection of medial frontal lesions may present transient postoperative speech disorders that remain largely unpredictable. OBJECTIVE: To relate the occurrence of this speech deficit to the specific surgical lesion of the supplementary motor area (SMA) involved during language tasks using fMRI. METHODS: Twelve patients were studied using a verbal fluency task before resection of a low-grade glioma of the medial frontal lobe and compared with six healthy subjects. Pre- and postoperative MR variables including the hemispheric dominance for language, the extent of SMA removal, and the volume of resection were compared to the clinical outcome. RESULTS: Following surgery, 6 of 12 patients presented speech disorders. The deficit was similar across patients, consisting of a global reduction in spontaneous speech, ranging from a complete mutism to a less severe speech reduction, which recovered within a few weeks or months. The occurrence of the deficit was related to the resection of the activation in the SMA of the dominant hemisphere for language (p < 0.01). Increased activation in the SMA of the healthy hemisphere on the preoperative fMRI was observed in patients with postoperative speech deficit. CONCLUSIONS: fMRI is able to identify the area at risk in the SMA, of which resection is related to the occurrence of characteristic transient postoperative speech disorders. Increased SMA activation in the healthy hemisphere suggested that a plastic change of SMA function occurred in these patients.
Adult↗
Antisaccade deficit after anterior cingulate cortex resection.
Suppression of unwanted reflexive saccades is a crucial process allowing to sustain voluntary fixation, when required. This inhibition process, which is mainly controlled by the dorsolateral prefrontal cortex, may also involve other cortical and subcortical structures. We prospectively studied the effect of frontal cortical resections involving adjacent regions to the anterior cingulate cortex on the ability to inhibit reflexive saccades. This lesion study included six patients undergoing resection of frontal low grade gliomas, studied prior and after surgery with electro-oculography, using the antisaccade paradigm. Lesions were normalized and mapped in Talairach space allowing to detail the structures whose lesions were associated with antisaccade deficits. In three of the six patients significant early post-operative antisaccade errors were associated with resection of a common critical region, mainly involving the posterior part of the anterior cingulate cortex. This same region was spared in the three remaining patients with no antisaccade deficit, suggesting that the anterior cingulate cortex, known as the cingulate eye field, could play a role in suppression of unwanted saccades.
Adult↗
Basal ganglia and supplementary motor area subtend duration perception: an fMRI study.
Brain imaging studies on duration perception usually report the activation of a network that includes the frontal and mesiofrontal cortex (supplementary motor area, SMA), parietal cortex, and subcortical areas (basal ganglia, thalamus, and cerebellum). To address the question of the specific involvement of these structures in temporal processing, we contrasted two visual discrimination tasks in which the relevant stimulus dimension was either its intensity or its duration. Eleven adults had to indicate (by pressing one of two keys) whether they thought the duration or the intensity of a light (LED) was equal to (right hand) or different from (left hand) that of a previously presented standard. In a control task, subjects had to press one of the two keys at random. A similar broad network was observed in both the duration-minus-control and intensity-minus-control comparisons. The intensity-minus-duration comparison pointed out activation in areas known to participate in cognitive operations on visual stimuli: right occipital gyrus, fusiform gyri, hippocampus, precuneus, and intraparietal sulcus. In contrast, the duration-minus-intensity comparison indicated activation of a complex network that included the basal ganglia, SMA, ventrolateral prefrontal cortex, inferior parietal cortex, and temporal cortex. These structures form several subnetworks, each possibly in charge of specific time-coding operations in humans. The SMA and basal ganglia may be implicated in the time-keeping mechanism, and the frontal-parietal areas may be involved in the attentional and mnemonic operations required for encoding and retrieving duration information.
Adult↗
Visual word recognition in the left and right hemispheres: anatomical and functional correlates of peripheral alexias.
According to a simple anatomical and functional model of word reading, letters displayed in one hemifield are first analysed through a cascade of contralateral retinotopic areas, which compute increasingly abstract representations. Eventually, an invariant representation of letter identities is created in the visual word form area (VWFA), reproducibly located within the left occipito-temporal sulcus. The VWFA then projects to structures involved in phonological or lexico-semantic processing. This model yields detailed predictions on the reading impairments that may follow left occipitotemporal lesions. Those predictions were confronted to behavioural, anatomical and functional MRI data gathered in normals and in patients suffering from left posterior cerebral artery infarcts. In normal subjects, alphabetic stimuli activated both the VWFA and the right-hemispheric symmetrical region (R-VWFA) relative to fixation, but only the VWFA showed a preference for alphabetic strings over simple chequerboards. The comparison of normalized brain lesions with reading-induced activations showed that the critical lesion site for the classical syndrome of pure alexia can be tightly localized to the VWFA. Reading impairments resulting from deafferentation of an intact VWFA from right- or left-hemispheric input were dissected using the same methods, shedding light on the connectivity of the VWFA. Finally, the putative role of right-hemispheric processing in the letter-by-letter reading strategy was clarified. In a letter-by-letter reader, the R-VWFA assumed some of the functional properties normally specific to the VWFA. These data corroborate our initial model of normal word perception and underline that an alternative right-hemispheric pathway can underlie functional recovery from alexia.
Adult↗
[Dystonia: contributions of functional imaging and magnetoencephalography].
Functional neuroimaging using positron emission tomography (PET), and more recently functional MRI (fMRI) and magnetoencephalography (MEG), is a valuable tool to study functional anomalies in dystonia. Activation studies have contributed to a better understanding of cerebral dysfunction in dystonia showing two main types of abnormalities: changes in activation levels during performance of sensory or motor tasks and disorganization of the selectivity of neuronal representations. In primary dystonia, most PET and fMRI studies have shown overactivity in premotor and prefrontal areas and underactivation of primary sensorimotor areas. In secondary dystonia, premotor and prefrontal areas are similarly overactive as well as primary sensorimotor areas. Altered selectivity of neuronal representations has been described more recently along cortico-subcortical circuits. The loss of neuronal selectivity may contribute to the loss of selectivity of muscular contractions observed in dystonia. Spectroscopic MRI may also be used to measure GABA levels, which are decreased in the cortex and basal ganglia in these patients.
Animals↗
Visualizing the neural bases of a disconnection syndrome with diffusion tensor imaging.
Disconnection syndromes are often conceptualized exclusively within cognitive box-and-arrow diagrams unrelated to brain anatomy. In a patient with alexia in his left visual field resulting from a posterior callosal lesion, we illustrate how diffusion tensor imaging can reveal the anatomical bases of a disconnection syndrome by tracking the degeneration of neural pathways and relating it to impaired fMRI activations and behavior. Compared to controls, an abnormal pattern of brain activity was observed in the patient during word reading, with a lack of activation of the left visual word form area (VWFA) by left hemifield words. Statistical analyses of diffusion images revealed a damaged fiber tract linking the left ventral occipito-temporal region to its right homolog across the lesioned area of corpus callosum and stopping close to the areas found active in fMRI. The behavioral disconnection syndrome could, thus, be related functionally to abnormal fMRI activations and anatomically to the absence of a connection between those activations. The present approach, based on the "negative tracking" of degenerated bundles, provides new perspectives on the understanding of human brain connections and disconnections.
Adult↗
Clinical characteristics and topography of lesions in movement disorders due to thalamic lesions.
OBJECTIVE: To determine which thalamic subnuclei are involved in symptomatic unilateral movement disorders due to localized thalamic infarction, and the clinical characteristics of these abnormal movements. METHODS: The authors studied 22 patients with thalamic infarcts for their clinical presentation and the topography of the lesions, using three-dimensional T1-weighted MRI sequencing and stereotaxic analysis of the lesions. RESULTS: Patients were divided into four groups: 1) absence of abnormal involuntary movements (AIM) (nine patients); 2) isolated dystonic posture (two patients); 3) myoclonic dystonia (five patients); and 4) tremor or myoclonus (six patients). In patients with AIM, thalamic lesions were contralateral to the abnormal movements, involving the thalamogeniculate territory, centered on the ventral intermediate (Vim) and ventral caudal (Vc) nuclei. No significant difference in the volumes or center of mass of the lesions was found between patients with tremor and myoclonus and patients with dystonia, although the central nucleus and the internal part of the Vim nucleus were more consistently damaged in dystonic patients. CONCLUSION: Movement disorders related to thalamic lesions included: 1) myoclonic dystonia with predominating myoclonus and "thalamic" hand associating dystonic posture and slow, pseudo-athetoid movements, both related to lesions in the Vim and Vc nuclei of the thalamus; and 2) postural and action tremor, also related to lesions in the Vim, similar to tremor associated with midbrain lesions, as a result of abnormal functioning of the cerebello-thalamic pathways.
Aged↗
Role of the supplementary motor area in motor deficit following medial frontal lobe surgery.
OBJECTIVE: Patients undergoing surgical resection of medial frontal lesions may present a transient postoperative deficit that remains largely unpredictable. The authors studied the role of the supplementary motor area (SMA) in the occurrence of this deficit using fMRI. METHODS: Twenty-three patients underwent a preoperative fMRI before resection of medial frontal lesions. Tasks included self-paced flexion/extension of the left and right hand, successively. Preoperative fMRI data were compared with postoperative MRI data and with neurologic outcome. RESULTS: Following surgery, 11 patients had a motor deficit from which all patients recovered within a few weeks or months. The deficit was similar across patients, consisting of a global reduction in spontaneous movements contralateral to the operated side with variable severity. SMA activation was observed in all patients. The deficit was observed when the area activated in the posterior part of the SMA (SMA proper) was resected. CONCLUSIONS: fMRI is able to identify the area at risk in the SMA proper whose resection is highly related to the occurrence of the motor deficit. The clinical characteristics of this deficit support the role of the SMA proper in the initiation and execution of the movement.
Adult↗
Functional compensation of the left dominant insula for language.
The left dominant insula was recently described as an essential area of speech, inducing definitive language disturbances when injured. We describe a patient with mild dysphasia, harboring a left insular glioma. A functional MRI found activations within the left inferior and middle frontal gyri, superior temporal gyrus, basal ganglia, but not in the insula. Surgery was performed using intraoperative electrical mapping in the awake patient, identifying the same language sites as showed by fMRI. A complete glioma resection was then performed. Despite an entire dominant insula removal, the patient presented no postoperative deficit, and even recovered from the preoperative dysphasia. This case illustrates the brain ability to maintain normal language without the left insula. The mechanisms of compensation are discussed.
Adult↗
Human brain mapping in dystonia reveals both endophenotypic traits and adaptive reorganization.
Dystonia has a wide clinical spectrum from early-onset generalized to late-onset sporadic, task-specific forms. The genetic origin of the former has been clearly established. A critical role of repetitive skilled motor tasks has been put forward for the latter, while underlying vulnerability traits are still being searched for. Using magnetoencephalography, we looked for structural abnormalities reflecting a preexisting dysfunction. We studied finger representations of both hands in the primary sensory cortex, as compared in 23 patients with unilateral task-specific dystonia and 20 control subjects. A dramatic disorganization of the nondystonic hand representation was found in all patients, and its amount paralleled the severity of the dystonic limb motor impairment. Abnormalities were also observed in the cortex coding the dystonic limb representation, but they were important only in the most severely affected patients. The abnormal cortical finger representations from the nondystonic limb appear to be endophenotypic traits of dystonia. That finger representations from the dystonic limb were almost normal for the less severely affected patients may be due to intrinsic beneficial remapping in reaction against the primary disorder.
Adaptation, Physiological↗
Delayed verbal memory retrieval: a functional MRI study in epileptic patients with structural lesions of the left medial temporal lobe.
In a previous functional magnetic resonance imaging (fMRI) study, we suggested that in left medial temporal lobe epilepsy (LTLE) poor verbal episodic memory performances were sustained by abnormal neocortical and mesiotemporal activations. In the present study, we attempted to examine the evolution of these abnormal neocortical and mesiotemporal activations over 24 h. We thus observed the fMRI brain regions activated during the 24-h-delayed retrieval of a word list in the same sample of healthy control subjects and LTLE patients. In control subjects, a similar left occipitotemporofrontal network was activated during both immediate and 24-h-delayed retrieval conditions. In addition, the 24-h-delayed retrieval also activated a larger parietal region and the right hippocampus. This distributed neocortical and mesiotemporal network was very poorly activated during the 24-h-delayed retrieval in LTLE patients, suggesting the inability to reactivate areas that are keys to retrieving stored information.
Adolescent↗
The role of dorsolateral prefrontal cortex in the preparation of forthcoming actions: an fMRI study.
The dorsolateral prefrontal cortex (DLPFC) plays a key role in working memory (WM). Yet its precise contribution (the storage, manipulation and/or utilization of information for the forthcoming response) remains to be determined. To test the hypothesis that the DLPFC is more involved in the preparation of actions than in the maintenance of information in short-term memory (STM), we undertook a functional magnetic resonance imaging investigation in normal subjects performing two delayed response tasks (matching and reproduction tasks) in a visuospatial task sequence (presentation, delay, response). In the two tasks, the presentation and delay phases were similar, but the expected response was different: in the matching task, subjects had to indicate whether a visuospatial sequence matched the sequence presented before the delay period; in the reproduction task, subjects had to reproduce the sequence and, therefore, to mentally organize their response during the delay. Using a fMRI paradigm focusing on the delay period, we observed a significant DLPFC activation when subjects were required to mentally prepare a sequential action based on the information stored in STM. When subjects had only to maintain a visuospatial stimulus in STM, no DLPFC activation was found. These results suggest that a parietal-premotor network is sufficient to store visuospatial information in STM whereas the DLPFC is involved when it is necessary to mentally prepare a forthcoming sequential action based on the information stored in STM.
Adult↗