Dissociable frontal controls during visible and memory‐guided eye‐tracking of moving targets

When tracking visible or occluded moving targets, several frontal regions including the frontal eye fields (FEF), dorsal‐lateral prefrontal cortex (DLPFC), and anterior cingulate cortex (ACC) are involved in smooth pursuit eye movements (SPEM). To investigate how these areas play different roles in predicting future locations of moving targets, 12 healthy college students participated in a smooth pursuit task of visual and occluded targets. Their eye movements and brain responses measured by event‐related functional MRI were simultaneously recorded. Our results show that different visual cues resulted in time discrepancies between physical and estimated pursuit time only when the moving dot was occluded. Visible phase velocity gain was higher that that of occlusion phase. We found bilateral FEF association with eye‐movement whether moving targets are visible or occluded. However, the DLPFC and ACC showed increased activity when tracking and predicting locations of occluded moving targets, and were suppressed during smooth pursuit of visible targets. When visual cues were increasingly available, less activation in the DLPFC and the ACC was observed. In addition, there was a significant hemisphere effect in DLPFC, where right DLPFC showed significantly increased responses over left when pursuing occluded moving targets. Correlation results revealed that DLPFC, the right DLPFC in particular, communicates more with FEF during tracking of occluded moving targets (from memory). The ACC modulates FEF more during tracking of visible targets (likely related to visual attention). Our results suggest that DLPFC and ACC modulate FEF and cortical networks differentially during visible and memory‐guided eye tracking of moving targets. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.     

Rett syndrome: Controlled study of an oral opiate antagonist,naltrexone

Hypothesis: The opiate antagonist, naltrexone, will be beneficial in Rett syndrome. Subjects: Twenty-five individuals fulfilling the criteria for Rett syndrome. Method: Randomized, double-blind, placebo-controlled crossover trial with two treatment periods, 4 months each, and an intervening 1-month washout period. Clinical stage, motor and cognitive development, motor–behavioral analysis, neurophysiological parameters (computerized electroencephalographic analysis, breathing characteristics, quantification of stereotyped hand movements, and sleep characteristics), and cerebrospinal fluid β-endorphin measurements were evaluated at baseline and at the end of each treatment period. Results: Only data from the first period of this study were analyzed due to significant sequence effects in the crossover design. This analysis indicated positive effects on certain respiratory characteristics including decreased disorganized breathing during wakefulness. Four (40%) of the individuals receiving naltrexone progressed one or more clinical stages versus none of the individuals receiving placebo. The adjusted (for baseline value and Rett stage) end of treatment psychomotor test age (Bayley Scales) was significantly higher for the placebo group. There was no significant change for the other parameters. Conclusion: Naltrexone may modify some of the respiratory disturbance in Rett syndrome. Declines in motor function and more rapid progression of the disorder suggest a deleterious effect.     

The development of visual- and auditory processing in Rett syndrome: an ERP study

Rett syndrome is a neurodevelopmental disorder that occurs almost exclusively in females. It is characterized by a progressive loss of intellectual functioning and motor skills, and the development of stereotypic hand movements, that occur after a period of normal development. Event-related potentials were recorded to a passive auditory- and visual oddball task in 17 females with Rett syndrome aged between 2 and 60 years, and age-matched controls. Overall the participants with Rett syndrome had longer ERP latencies and smaller ERP amplitudes than the Control group suggesting slowed information processing and reduced brain activation. The Rett groups also failed to show typical developmental changes in event-related brain activity and revealed a marked decline in ERP task modulation with increasing age.     

Riser’s reflux – an eye‐opening experience

Background Patients with gastro‐oesophageal reflux disease (GORD) commonly report waking up in the morning with a sour or bitter taste in their mouth. The aim of the study was to compare the prevalence and frequency of acid reflux events prior to and immediately after awakening from sleep in the morning between GORD patients and normal subjects. Methods Thirty‐nine patients with heartburn at least three times a week and abnormal pH test and nine healthy controls were included. All subjects were evaluated by demographic and GORD Symptom Checklist questionnaires. Subjects underwent pH testing concomitantly with actigraphy. A novel technology that simultaneously integrates raw actigraphy and pH monitoring data was utilized to determine the presence, frequency, and characteristics of acid reflux events prior to (up to 1 h) and immediately after (10 and 20 min) awakening from sleep in the morning. Key Results Nineteen (48.7%) of the GORD patients had an acid reflux event within the first 20 min after awakening from sleep in the morning as compared to only seven (17.9%) during the hour prior to awakening. Within the first 10 and 20 min after awakening, patients had a total of 32 and 60 acid reflux events, respectively, as compared to 14 during the 1 h prior to awakening (P < 0.05). None of the healthy control patients demonstrated any reflux events during these three studied periods (P < 0.001). Conclusions & Inferences Riser’s reflux is very common among GORD patients and possibly may explain reports of early‐morning GORD symptoms.     

Frontal lobe disinhibition, Rett syndrome and attention deficit hyperactivity disorder.

Motor cortex hyperexcitability in Rett Syndrome (RS) has been ascribed to the failure of an inhibiting system arising from the frontal lobes, a system needed in childhood and early adolescence. It is also presumed that, on a virtually dysfunctional (nonstructural) basis, motor cortex hyperexcitability in ADHD is also due to insufficient frontal lobe inhibition ("lazy frontal lobe"). A series of schematic illustrations is added for the sake of easier comprehension of the presented concept.     

Perceptual and semantic familiarity in recognition memory: an event-related potential study

Putative event-related potential correlates of perceptual and semantic bases of familiarity in recognition memory were examined with a categorized pictures recognition test. Our participants were presented, at study, with pictures of categorized objects and, at test, with either the very same pictures presented at study, different pictures of studied objects, pictures of new objects belonging to studied categories, or pictures of completely new-uncategorized objects. We found evidence for a parallel evaluation, within familiarity process, of both perceptual and semantic information. We also found new and interesting evidence for the existence of some common neural circuits involved in the FN400 effect, frontal component typically associated to familiarity, and the N400 effect, centro-parietal component typically elicited by 'semantically unexpected' linguistic stimuli.     

Rett syndrome: retrospective and prospective study of 28 patients]

From November 1982 to May 1999, 28 children with Rett syndrome were followed-up for a medium period of 6 years and 2 months. Regression of developmental milestones started at the age between 5 and 20 months. Nineteen cases of typical Rett syndrome had uneventful pre and perinatal periods, loss of previously acquired purposeful hand skills, mental and motor regression and developed hand stereotypies; sixteen had head growth deceleration and 12 gait apraxia. Nine patients were atypical cases, 2 formes frustres, 2 congenital, 3 with early seizure onset, 1 preserved speech and 1 male. Epilepsy was present in 21 patients, predominantly partial seizures and the drug of choice was carbamazepine (15 patients). In the initial evaluation most patients were distributed on Stages II and III and on follow-up on Stages III and IV. Three children died.     

Associative memory encoding and recognition in schizophrenia: an event-related fMRI study.

BACKGROUND: We used an event-related functional Magnetic Resonance Imaging (fMRI) approach to examine the neural basis of the selective associative memory deficit in schizophrenia. METHODS: Fifteen people with schizophrenia and 18 controls were scanned during a pair and item memory encoding and recognition task. During encoding, subjects studied items and pairs of visual objects. In a subsequent retrieval task, participants performed an item recognition memory test (old/new decisions) and an associative recognition test (intact/rearranged decisions). The fMRI analysis of the recognition data was restricted to correct items only and a random effects model was used. RESULTS: At the behavioral level, both groups performed equally well on item recognition, whereas people with schizophrenia demonstrated lower performance on associative recognition relative to the control group. At the brain level, the comparison between associative and item encoding revealed greater activity in the control group in the left prefrontal cortex and cingulate gyrus relative to the schizophrenia group. During recognition, greater left dorsolateral prefrontal and right inferior prefrontal activations were observed in the control group relative to the schizophrenia group. CONCLUSION: This fMRI study implicates the prefrontal cortex among other brain regions as the basis for the selective associative memory encoding and recognition deficit seen in schizophrenia.     

Muscle—eye—brain disease: A neuropathological study

A combination of congenital central nervous, ocular and muscular abnormalities is characteristic of muscle—eye—brain disease (MEB), of Fukuyama congenital muscular dystrophy (FCMD), and of Walker-Warburg syndrome (WWS). The nosological relationship of these inherited malformative disorders is still unestablished, although the genetic locus for FCMD has been excluded in MEB. We present the first postmortem neuropathological study of MEB based on 2 male patients. Apart from sharply limited occipital agyric areas, their brain showed coarse gyri with an abnormally nodular surface (?cobblestone cortex”?). Both the cerebral and cerebellar cortices showed a total disorganization without horizontal lamination. The haphazardly oriented cortcal neurons formed irregular custers or islands, separated by gliovascular strands extending from the pia. The ocular abnormalities included a pronounced glial preretinal membrane. Although MEB shares the cobblestone cortex—type malformation with FCMD and WWS, the cerebral and ocular manifestations are less severe than in WWS. Furthermore, a consistently weak staining for laminin α2 chain (merosin) was found in muscle biopsy specimens from 4 MEB patients, while normal immunoreactivity was observed for the laminin α2 chain, reported to be severely deficient in WWS. These finding support nosological independence of MEB.     

Spontaneous pre‐stimulus oscillatory activity shapes the way we look: A concurrent imaging and eye‐movement study

Previous behavioural studies have accrued evidence that response time plays a critical role in determining whether selection is influenced by stimulus saliency or target template. In the present work, we investigated to what extent the variations in timing and consequent oculomotor controls are influenced by spontaneous variations in pre‐stimulus alpha oscillations. We recorded simultaneously brain activity using magnetoencephalography (MEG) and eye movements while participants performed a visual search task. Our results show that slower saccadic reaction times were predicted by an overall stronger alpha power in the 500 ms time window preceding the stimulus onset, while weaker alpha power was a signature of faster responses. When looking separately at performance for fast and slow responses, we found evidence for two specific sources of alpha activity predicting correct versus incorrect responses. When saccades were quickly elicited, errors were predicted by stronger alpha activity in posterior areas, comprising the angular gyrus in the temporal‐parietal junction (TPJ) and possibly the lateral intraparietal area (LIP). Instead, when participants were slower in responding, an increase of alpha power in frontal eye fields (FEF), supplementary eye fields (SEF) and dorsolateral pre‐frontal cortex (DLPFC) predicted erroneous saccades. In other words, oculomotor accuracy in fast responses was predicted by alpha power differences in more posterior areas, while the accuracy in slow responses was predicted by alpha power differences in frontal areas, in line with the idea that these areas may be differentially related to stimulus‐driven and goal‐driven control of selection.     

Cerebrolysin therapy in Rett syndrome: clinical and EEG mapping study

Based on the suggestion that nerve growth factor plays a core role in the brain maturation process, which is altered in Rett syndrome, we investigate the influence of Cerebrolysin — the brain-derived peptidergic drug — on motor and higher cortical functions in Rett syndrome girls. The open pilot study was performed on nine Rett syndrome girls (aged from 2 years and 2 months to 7 years and 6 months) at stage 3 of the illness, and included both clinical and quantitative EEG evaluations before and after Cerebrolysin treatment. After Cerebrolysin treatment, increases in the behavioral activity, attention level, motor functions, and non-verbal social communication have been shown in Rett syndrome patients. EEG parameters after Cerebrolysin treatment also changed towards normal values, indicating an improvement of the brain functional state. EEG changes included: decrease of theta activity over all cortical regions, increase of beta activity in the frequency band 13–15 Hz, and some restoration of the occipital alpha rhythm (in the narrow 8–9 Hz band). The data obtained suggested possible perspectives of Cerebrolysin in complex therapy of Rett syndrome.     

False recognition in a verbal memory task: an event-related potential study

Brain potentials were recorded from 15 healthy young subjects during the performance of a word recognition task. During the study phase, subjects had to intentionally memorise a series of words. These words were presented again together with the same number of new words in a following test phase where the instruction was to discriminate between repeated words and new words. We compared event-related potentials (ERPs) evoked by correctly identified repeated words (hits) and ERPs evoked by incorrectly classified new words (false alarms). Although both types of words were thought to be repeated the ERPs indicated differences between these two conditions starting at about 450 ms after the stimulus onset. These differences were mostly pronounced over frontal scalp locations but occurred also over parietal scalp locations (false alarms produced significantly more negative going ERPs than hits). We interpret that frontal and parietal brain areas show greater activation during false recognition because of a more intensive search for item representations.     

Further dissociating the processes involved in recognition memory: an FMRI study

Based on an event-related potential study by Rugg et al. [Dissociation of the neural correlates of implicit and explicit memory. Nature, 392, 595-598, 1998], we attempted to isolate the hemodynamic correlates of recollection, familiarity, and implicit memory within a single verbal recognition memory task using event-related fMRI. Words were randomly cued for either deep or shallow processing, and then intermixed with new words for yes/no recognition. The number of studied words was such that, whereas most were recognized ("hits"), an appreciable number of shallow-studied words were not ("misses"). Comparison of deep hits versus shallow hits at test revealed activations in regions including the left inferior parietal gyrus. Comparison of shallow hits versus shallow misses revealed activations in regions including the bilateral intraparietal sulci, the left posterior middle frontal gyrus, and the left frontopolar cortex. Comparison of hits versus correct rejections revealed a relative deactivation in an anterior left medial-temporal region (most likely the perirhinal cortex). Comparison of shallow misses versus correct rejections did not reveal response decreases in any regions expected on the basis of previous imaging studies of priming. Given these and previous data, we associate the left inferior parietal activation with recollection, the left anterior medial-temporal deactivation with familiarity, and the intraparietal and prefrontal responses with target detection. The absence of differences between shallow misses and correct rejections means that the hemodynamic correlates of implicit memory remain unclear.     

Rett syndrome: a case report from an audiovisual program

A case report of a 13-yr-6-mo-old girl with the Rett syndrome is provided from an audiovisual program featuring home movies taken from 2 mos of age and onward. The patient shows the following symptoms not previously emphasized in the Rett syndrome: deceleration of head growth (rather than acquired microcephaly), fall-off in linear growth in infancy, early hypotonia, precocious puberty and respiratory alkalosis. Except for the precocious puberty, a second, 35-mo-old, patient has followed the same clinical course with similar laboratory findings.     

Morphological study of neocortical areas in Rett syndrome

Various neocortical areas from four females aged 16–24 years with Rett syndrome (RS) were investigated and compared with brains of therapy-resistant partial epilepsy (TRPE) patients (18–25 years), infantile autism (IA), and control brains (24 and 58 years). The cytoarchitecture of area 10 (frontal), area 21 (temporal), area 4 (primary motor cortex), and area 17 (primary visual cortex) was studied by the combined Klüver-Barrera (luxol fast blue and cresyl violet) standard procedure. Autofluorescence of lipofuscin, immunofluorescence of synaptic vesicle proteins [synaptophysin (p38)] and lectin-stained (Wisteria floribunda agglutinin) perineuronal nets (PNs) were studied in the cortices using dual-channel confocal laser scanning microscopy. The brains of RS females show various types of morphological/cytoarchitectonical abnormalities of single pyramidal neurons in layers II–III, and V–VII of different cortical areas. The abnormalities include mild losses of pyramidal neurons, more pronounced in layers II and III than in layers V and VII, and more evident in frontal and temporal areas than in the visual cortex. Microdysgenesis, including abnormalities due to neuronal migration disorders, was not found in RS, in contrast to the observations in TRPE patients, strongly indicating that RS is not a neuronal migration disorder. Lipofuscin distribution was normal but amounts were lower in RS cases than in control and TRPE brains. PNs were less expressed in cortices of the IA case, but were clearly overexpressed in the motor cortex of RS. Quantitative analysis of p38 showed a decrease in the area occupied by p38 immunoreactivity by 20–40% in RS compared with controls. It is concluded that RS could best be explained by a postnatal synaptogenic developmental deficiency; the basic defect, however, is still completely unknown. Received: 26 February 1996 / Revised, accepted: 11 July 1996