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Functional MRI study of diencephalic amnesia in Wernicke-Korsakoff syndrome.

Anterograde amnesia in Wernicke-Korsakoff syndrome is associated with diencephalic lesions, mainly in the anterior thalamic nuclei. Whether diencephalic and temporal lobe amnesias are distinct entities is still not clear. We investigated episodic memory for faces using functional MRI (fMRI) in eight controls and in a 34-year-old man with Wernicke-Korsakoff syndrome and diencephalic lesions but without medial temporal lobe (MTL) involvement at MRI. fMRI was performed with a 1.5 tesla unit. Three dual-choice tasks were employed: (i) face encoding (18 faces were randomly presented three times and subjects were asked to memorize the faces); (ii) face perception (subjects indicated which of two faces matched a third face); and (iii) face recognition (subjects indicated which of two faces belonged to the group they had been asked to memorize during encoding). All activation was greater in the right hemisphere. In controls both the encoding and recognition tasks activated two hippocampal regions (anterior and posterior). The anterior hippocampal region was more activated during recognition. Activation in the prefrontal cortex was greater during recognition. In the subject with Wernicke-Korsakoff syndrome, fMRI did not show hippocampal activation during either encoding or recognition. During recognition, although behavioural data showed defective retrieval, the prefrontal regions were activated as in controls, except for the ventrolateral prefrontal cortex. fMRI activation of the visual cortices and the behavioural score on the perception task indicated that the subject with Wernicke-Korsakoff syndrome perceived the faces, paid attention to the task and demonstrated accurate judgement. In the subject with Wernicke-Korsakoff syndrome, although the anatomical damage does not involve the MTL, the hippocampal memory encoding has been lost, possibly as a consequence of the hippocampal-anterior thalamic axis involvement. Anterograde amnesia could therefore be the expression of damage to an extended hippocampal system, and the distinction between temporal lobe and diencephalic amnesia has limited value. In the subject with Wernicke-Korsakoff syndrome, the preserved dorsolateral prefrontal cortex activation during incorrect recognition suggests that this region is more involved in either the orientation or attention at retrieval than in retrieval. The lack of activation of the prefrontal ventrolateral cortex confirms the role of this area in episodic memory formation.

Adult↗

Functional MRI in healthy subjects during acupuncture: different effects of needle rotation in real and false acupoints.

The cerebral activation pattern due to acupuncture is not completely understood. Although the effect of acupuncture on cerebral haemodynamics has been studied, no previous report has focused on different puncture and stimulation methods. We used functional MRI (fMRI) in 15 healthy subjects to investigate cortical activation during stimulation of two real acupoints (Liv3 and G40) and one sham point, needled in a random and, for the subjects, blinded order employing rotating and non-rotating methods, using a blocked paradigm on a 1.5 tesla imager. Compared to the non-rotating stimulation method, during rotating stimulation of the real acupoints, we observed an increase in activation in both secondary somatosensory cortical areas, frontal areas, the right side of the thalamus and the left side of the cerebellum; no such effects of the needling technique were seen while stimulating the sham point. The observation that rotating the needle strengthened the effects of acupuncture only at real acupoints suggests that, as claimed in Chinese traditional medicine, stimulation of these acupoints has a specific effect on cortical neuronal activity, absent with sham acupoints. These specific cerebral activation patterns might explain the therapeutic effects of acupuncture in certain subjects.

Acupuncture Therapy↗

Functional MRI of motor sequence acquisition: effects of learning stage and performance.

Neural networks of motor control are well understood and the motor domain therefore lends itself to the study of learning. Neuroimaging of motor learning has demonstrated fronto-parietal, subcortical, and cerebellar involvement. However, there is conflicting evidence on the specific functional contributions of individual regions and their relative importance for early and advanced stages of learning. Using functional MRI (fMRI), we examined hemodynamic effects in seven right-handed men during brief episodes of explicit learning of novel six-digit sequences (experiments 1 and 2) and during prolonged learning of an eight-digit sequence (experiment 3), all performed with the dominant hand. Brief episodes of new learning were predominantly associated with bilateral activations in premotor and supplementary motor areas, superior and inferior parietal cortices, and anterior cerebellum. In experiment 2, which included a control condition matched for complexity of motor execution, we also found unexpectedly strong activation in the bilateral inferior frontal lobes. In experiment 3, analysis of task by learning stage interactions showed greater involvement of the bilateral superior parietal lobes, the right middle frontal gyrus, and the left caudate nucleus during early stages, whereas left occipito-temporal and superior frontal cortex as well as the bilateral parahippocampal region were more activated during late learning stages. Analysis of task by performance interactions (based on each subject's response times and accuracy during each scan) showed effects in bilateral fronto-polar, right hippocampal, and anterior cerebellar regions associated with high levels of performance, as well as inverse effects in bilateral occipito-parietal regions. We conclude that superior parietal and occipital regions are most intensely involved in visually driven explicit digit sequence learning during early stages and low performance, whereas later stages of acquisition and higher levels of performance are characterized by stronger recruitment of prefrontal and mediotemporal regions.

Adult↗

GABAergic mechanisms of heroin-induced brain activation assessed with functional MRI.

Heroin has been hypothesized to activate opiate receptors and inhibit gamma-aminobutyric acid (GABA) release from inhibitory GABAergic interneurons which, in turn, activates dopamine projection cells. Since the distal sites and consequences of this disinhibition are not well understood on a systems level, heroin-induced brain activity was measured using functional MRI (fMRI) in rats. A significant blood oxygen level-dependent (BOLD) signal increase was seen in cortical regions, including prefrontal cortex, cingulate, and olfactory cortex following acute heroin administration. In contrast, a significant signal decrease was seen in several subcortical areas, including the caudate and putamen, nucleus accumbens, thalamus, and hypothalamus. Pretreatment of gamma-vinyl GABA (GVG), an irreversible GABA transaminase inhibitor, significantly attenuated the heroin-induced BOLD signal changes. Pretreatment of naloxone, an opiate mu receptor antagonist, eliminated the heroin-induced BOLD signal changes and posttreatment of naloxone reversed the heroin-induced BOLD signal changes. It is suggested that the heroin-induced negative and positive BOLD changes are due to direct inhibitory and indirect disinhibitory mechanisms of GABAergic activities. Administration of GVG altered these mechanisms and further suggested that involvement of the opiate's pharmacological actions can, at least in part, be mediated by inhibiting brain GABA release.

Analgesics, Opioid↗

Usefulness of motor functional MRI correlated to cortical mapping in Rolandic low-grade astrocytomas.

The indications for surgery of slow growing tumours like low grade astrocytomas in eloquent areas are difficult. The timing and the benefit/risk ratio of the surgery must be evaluated, taking into account the potential post operative deficit. The purpose of this study was: a) to validate the data obtained with functional MRI (FMRI) by direct cortical stimulation in patients who are candidate for surgery; b) to demonstrate the usefulness of FMRI coupled with cortical brain mapping and 3D reconstructions of the surfaces of the brain in low grade astrocytoma. FMRI of the hand-motor cortex was performed in 8 patients with low grade astrocytomas. They subsequently underwent direct cortical mapping to correlate the results of FMRI and resective surgery sparing the functional area. In the 8 cases, the results of direct cortical mapping in the precentral region matched accurately those obtained from FMRI. When surgical resection of low grade astrocytoma in the motor areas is considered, FMRI used with intra-operative cortical mapping can help the surgeon to spare functional areas during tumour removal.

Adult↗

Cerebral correlates of preserved cognitive skills in autism: a functional MRI study of embedded figures task performance.

When considering the cognitive abilities of people with autism, the majority of studies have explored domains in which there are deficits. However, on tests of local processing and visual search, exemplified by the Embedded Figures Task (EFT), people with autism have been reported to demonstrate superiority over normal controls. This study employed functional MRI of subjects during the performance of the EFT to test the hypothesis that normal subjects and a group with autism would activate different brain regions and that differences in the patterns of these regional activations would support distinct models of cerebral processing underlying EFT performance in the two groups. It was found that several cerebral regions were similarly activated in the two groups. However, normal controls, as well as demonstrating generally more extensive task-related activations, additionally activated prefrontal cortical areas that were not recruited in the group with autism. Conversely, subjects with autism demonstrated greater activation of ventral occipitotemporal regions. These differences in functional anatomy suggest that the cognitive strategies adopted by the two groups are different: the normal strategy invokes a greater contribution from working memory systems while the autistic group strategy depends to an abnormally large extent on visual systems for object feature analysis. This interpretation is discussed in relation to a model of autism which proposes a predisposition towards local rather than global modes of information processing.

Adult↗

Fixation-off sensitivity as a model of continuous epileptiform discharges: electroencephalographic, neuropsychological and functional MRI findings.

A case of fixation-off sensitivity (FOS) in an asymptomatic adult is presented and studied as a model for continuous epileptiform discharges. Video-electroencephalographic (EEG) revealed continuous bilateral occipital spike wave discharges during elimination of central vision, which were shown to be associated with transitory cognitive impairment demonstrated by neuropsychological testing. Functional MRI showed activation of parieto-occipital and frontal brain areas during the fixation-off discharges. This localization was confirmed with 64-channel EEG source analysis. The applied methods provided additional information on the pathophysiology of epileptiform discharges.

Adult↗

Premovement activity of the pre-supplementary motor area and the readiness for action: studies of time-resolved event-related functional MRI.

The supplementary motor area (SMA) is thought to play in important role in the preparation and organisation of voluntary movement. It has long been known that cortical activity begins to increase up to 2s prior to voluntary self-initiated movement. This increasing premovement activity measured in EEG is known as the Bereitschaftspotential or readiness potential. Modern functional brain imaging methods, using event-related and time-resolved functional MRI techniques, are beginning to reveal the role of the SMA, and in particular the more anterior pre-SMA, in premovement activity associated with the readiness for action. In this paper we review recent studies using event-related time-resolved fMRI methods to examine the time-course of activation changes within the SMA throughout the preparation, readiness and execution of action. These studies suggest that the pre-SMA plays a common role in encoding or representing actions prior to our own voluntary self-initiated movements, during motor imagery, and from the observation of others' actions. We suggest that the pre-SMA generates and encodes motor representations which are then maintained in readiness for action.

Arousal↗

[Hand motor cortical area reorganization following cerebral infarction evaluated with functional MRI, near infrared spectroscopic imaging, and transcranial magnetic stimulation].

A 60-year-old, right-handed man suffered from left hemiparesis with upper limb dominance. CT and MRI revealed cerebral infarction of the entire right middle cerebral artery territory. His hemiparesis recovered excellently and residual neurological deficits 6 years later were left hand weakness(grasping power 9 kg vs. 35 kg in the right) and clumsiness. Functional MRI was performed. During right(normal) hand grasping, activation was seen in the left sensorimotor cortex and supplementary motor area. During left(paretic) hand grasping, activation was seen in the left (ipsilateral) sensorimotor cortex, right parietal cortex, and bilateral supplementary motor areas. Near infrared spectroscopic imaging showed similar results. During right hand grasping, left sensorimotor cortex was activated, and during left hand grasping, bilateral sensorimotor cortices were activated with ipsilateral predominance. Transcranial magnetic stimulation of the left motor hand area evoked right hand movement and stimulation of a point near that area evoked ipsilateral left hand muscle movement. Thus, the findings of the three techniques consistently suggest that the recovery of left hemiparesis of this patient was promoted by motor cortical area reorganization including the ipsilateral motor cortex.

Brain↗

Mental chronometry using latency-resolved functional MRI.

Vascular responses to neural activity are exploited as the basis of a number of brain imaging techniques. The vascular response is thought to be too slow to resolve the temporal sequence of events involved in cognitive tasks, and hence, imaging studies of mental chronometry have relied on techniques such as the evoked potential. Using rapid functional MRI (fMRI) of single trials of two simple behavioral tasks, we demonstrate that while the microvascular response to the onset of neural activity is delayed consistently by several seconds, the relative timing between the onset of the fMRI responses in different brain areas appears preserved. We examined a number of parameters that characterize the fMRI response and determined that its onset time is best defined by the inflection point from the resting baseline. We have found that fMRI onset latencies determined in this manner correlate well with independently measurable parameters of the tasks such as reaction time or stimulus presentation time and can be used to determine the origin of processing delays during cognitive or perceptual tasks with a temporal accuracy of tens of milliseconds and spatial resolution of millimeters.

Brain↗

Brain activation during working memory 1 month after mild traumatic brain injury: a functional MRI study.

OBJECTIVE: To assess patterns of regional brain activation in response to varying working memory loads shortly after mild traumatic brain injury (MTBI). BACKGROUND: Many individuals complain of memory difficulty shortly after MTBI. Memory performance in these individuals can be normal despite these complaints. METHODS: Brain activation patterns in response to a working memory task (auditory n-back) were assessed with functional MRI in 12 MTBI patients within 1 month of their injury and in 11 healthy control subjects. RESULTS: Brain activation patterns differed between MTBI patients and control subjects in response to increasing working memory processing loads. Maximum intensity projections of statistical parametric maps in control subjects showed bifrontal and biparietal activation in response to a low processing load, with little additional increase in activation associated with the high load task. MTBI patients showed some activation during the low processing load task but significantly increased activation during the high load condition, particularly in the right parietal and right dorsolateral frontal regions. Task performance did not differ significantly between groups. CONCLUSION: MTBI patients differed from control subjects in activation pattern of working memory circuitry in response to different processing loads, despite similar task performance. This suggests that injury-related changes in ability to activate or to modulate working memory processing resources may underlie some of the memory complaints after MTBI.

Adult↗

Human medullary responses to cooling and rewarming the skin: a functional MRI study.

A fall in skin temperature precipitates a repertoire of thermoregulatory responses that reduce the likelihood of a decrease in core temperature. Studies in animals suggest that medullary raphé neurons are essential for cold-defense, mediating both the cutaneous vasoconstrictor and thermogenic responses to ambient cooling; however, the involvement of raphé neurons in human thermoregulation has not been investigated. This study used functional MRI with an anatomically guided region of interest (ROI) approach to characterize changes in the blood oxygen level-dependent (BOLD) signal within the human medulla of nine normal subjects during non-noxious cooling and rewarming of the skin by a water-perfused body suit. An ROI covering 4.9 +/- 0.3 mm(2) in the ventral midline of the medulla immediately caudal to the pons (the rostral medullary raphé) showed an increase in BOLD signal of 3.9% (P < 0.01) during periods of skin cooling, compared with other times. Overall, that signal showed a strong inverse correlation (R = 0.48, P < 0.001) with skin temperature. A larger ROI covering the internal medullary cross section at the same level (area, 126 +/- 15 mm(2)) showed no significant change in mean BOLD signal with cooling (+0.2%, P > 0.05). These findings demonstrate that human rostral medullary raphé neurons are selectively activated in response to a thermoregulatory challenge and point to the location of thermoregulatory neurons homologous to those of the raphé pallidus nucleus in rodents.

Adult↗

Functional MRI evidence for a role of frontal and inferior temporal cortex in amodal components of priming.

Changes in human brain activity associated with repetition priming during word generation were characterized across a series of neuroimaging and behavioural studies. Repetition priming was consistently observed behaviourally as a decrease in response latency for repeated items, and was found for both visually and aurally cued word-generation tasks. Brain imaging using whole-brain functional MRI identified neural correlates of these effects. The principal effect of priming was to reduce neural activity within regions that were already being used to perform the word-generation tasks. Repeated word generation in response to visual cues was correlated with anatomically selective reductions in activity within the left frontal cortex along the inferior frontal gyrus and inferior temporal regions and, to a lesser degree, in specific earlier visual regions. These reductions were reversed when new items were presented, indicating that they were item-specific. Repeated word generation in response to aural cues also showed anatomically selective activity reductions within the left frontal and inferior temporal regions, indicating that these activity reductions were not dependent on the perceptual modality of the cue. The auditory cortex showed minimal repetition-related reductions. The presence of activity within left frontal regions that decreases as a function of item repetition for both visual and auditory cues suggests that these reductions may underlie an amodal repetition-priming effect existing at processing stages involving lexical/semantic search and access. The surprising finding that activity reductions in the inferior temporal cortex can be linked to repetition of either visual or auditory cues further suggests that these regions may be modulated in a top-down fashion during repetition priming, independent of (or in parallel with) stimulus-driven perceptual processes. Taken collectively, the data converge on a neural correlate of lexical/semantic priming. Amodal lexical/semantic processes, which may be triggered initially by modality-specific cues, proceed via an interaction between frontal and posterior brain regions. These interdependent regions show activity reductions that correlate with facilitated task performance when items are repeated.

Acoustic Stimulation↗

Preliminary report: functional MRI of the brain may be the ideal tool for evaluating neuropsychologic and sleep complaints of patients with primary hyperparathyroidism.

BACKGROUND: The incidence, pattern, and severity of sleep disturbance and cognitive dysfunction has not been well characterized for patients with primary hyperparathyroidism (PHPT). There is no agreement on the mechanism of the development or resolution of such symptoms, and in no previous study has cerebral activity been functionally assessed and change documented following surgical cure of patients with PHPT. METHODS: We undertook a prospective analysis to obtain pilot data on 6 patients with PHPT. Functional magnetic resonance imaging (fMRI), formal neuropsychologic (NP) tests, and health-related quality of life (HRQL) measures that included sleep assessments were performed on patients before and after parathyroidectomy. Changes in cortical activation under both conflict and neutral conditions (distracting tasks) were recorded. RESULTS: Functional MRI demonstrated postoperative changes in medial prefrontal cortex activity during cognitive processing of conflict and nonconflict tasks. Further postoperative changes were noted in the dorsolateral prefrontal cortex and parietal cortex with shifts in activations. In addition to the fMRI findings, the patients demonstrated improvements in sleep and social behavior. They tended to experience less fatigue and their processing speed on cognitive tests improved. CONCLUSIONS: These data support the feasibility and willingness of patients with PHPT to undergo fMRI assessment. Preliminary findings reflected a generalized improvement in processing efficiency postoperatively compared with a patient's preoperative state, and the HRQL measures showed improved sleep. These findings mirror those expected with sleep dysfunction. Longitudinal assessment with advanced brain imaging technology, neuropsychological (NP), and sleep evaluations is warranted to further explore cognitive, sleep, and HRQL improvement after parathyroidectomy.

Adult↗

Functional MRI predicts post-surgical memory following temporal lobectomy.

Temporal lobectomy is an effective therapy for medically refractory temporal lobe epilepsy (TLE), but may be complicated by amnestic syndromes. Therefore, pre-surgical evaluation to assess the risk/benefit ratio for surgery is required. Intracarotid amobarbital testing (IAT) is currently the most widely used method for assessing pre-surgical memory lateralization, but is relatively invasive. Over the past decade functional MRI (fMRI) has been shown to correlate with IAT for language lateralization, and also for memory lateralization in a small number of patients. This study was carried out to compare fMRI during memory encoding with IAT testing for memory lateralization, and to assess the predictive value of fMRI during memory encoding for post-surgical memory outcome. Thirty-five patients with refractory TLE undergoing pre-surgical evaluation for temporal lobectomy and 30 normal subjects performed a complex visual scene-encoding task during fMRI scanning at 1.5 T using a 10-min protocol. Encoding performance was evaluated with subsequent recognition testing. Twenty-three patients also completed the same task again outside the scanner, an average of 6.9 months following surgery. A region of interest (ROI) analysis was used to quantify activation within hippocampal and a larger mesial temporal lobe ROI consisting of hippocampus, parahippocampus and fusiform gyrus (HPF) as defined by a published template. Normal subjects showed almost symmetrical activation within these ROI. TLE patients showed greater asymmetry. Asymmetry ratios (ARs) from the HPF ROI correlated significantly with memory lateralization by intracarotid amobarbital testing. HPF ARs also correlated significantly with memory outcome, as determined by a change in scene recognition between pre-surgical and post-surgical trials. When absolute activation within the HPF ROI was considered, a significant inverse correlation between activation ipsilateral to temporal lobectomy and memory outcome was observed, with no significant correlation in the contralateral HPF ROI. Although further technical improvements and prospective clinical validation are required, these results suggest that mesial temporal memory activation detected by fMRI during complex visual scene encoding correlates with post-surgical memory outcome and supports the notion that this approach will ultimately contribute to patient management.

Adult↗

BOLD-contrast functional MRI signal changes related to intermittent rhythmic delta activity in EEG during voluntary hyperventilation-simultaneous EEG and fMRI study.

Differences in the blood oxygen level dependent (BOLD) signal changes were studied during voluntary hyperventilation (HV) between young healthy volunteer groups, (1) with intermittent rhythmic delta activity (IRDA) (N = 4) and (2) controls (N = 4) with only diffuse arrhythmic slowing in EEG (normal response). Subjects hyperventilated (3 min) during an 8-min functional MRI in a 1.5-T scanner, with simultaneous recording of EEG (successful with N = 3 in both groups) and physiological parameters. IRDA power and average BOLD signal intensities (of selected brain regions) were calculated. Hypocapnia showed a tendency to be slightly lighter in the controls than in the IRDA group. IRDA power increased during the last minute of HV and ended 10-15 s after HV. The BOLD signal decreased in white and gray matter after the onset of HV and returned to the baseline within 2 min after HV. The BOLD signal in gray matter decreased approximately 30% more in subjects with IRDA than in controls, during the first 2 min of HV. This difference disappeared (in three subjects out of four) during IRDA in EEG. BOLD signal changes seem to depict changes, which precede IRDA. IRDA due to HV in healthy volunteers represent a model with a clearly defined EEG pattern and an observable BOLD signal change.

Adult↗

Informatics approaches to functional MRI odor mapping of the rodent olfactory bulb: OdorMapBuilder and OdorMapDB.

The present study applies informatics tools to aid and extend fMRI analysis of the coding mechanism of neural signals in the rodent olfactory system. Odor stimulation evokes unique spatial patterns of activity in the glomerular layer of the mammalian olfactory bulb (OB). An open-source software program, OdorMap-Builder, has been developed to process the high resolution anatomical and functional MRI images of the OB and to generate single two-dimensional flat maps, called odor maps, that describe the spatial activity patterns in the entire glomerular layer. Odor maps help identify the spatial activity patterns from the tremendous amount of fMRI data and they serve as ideal representation of space coding for the olfactory signals in the OB in response to a given odor stimulation. Based on the fMRI technology, OdorMapBuilder provides comparable odor maps on the intra-subject basis, a significant step towards the detailed analyses of the effects of odor types and/or concentrations. In addition, a new database, OdorMapDB, is developed to provide a repository for the generated odor maps. Web interfaces to the database are provided for the data entry, modification and retrieval. OdorMapDB is based on the EAV/CR (entity-attribute-value with classes and relationships) architecture and it is integrated with two other SenseLab olfactory databases: the olfactory receptor and odor databases. Both OdorMapBuilder and OdorMapDB should serve as useful tools and resources for the field and help facilitate experimental research in understanding the olfactory system and the mechanism for smell perception.

Animals↗