Disruption of attention to novel events after frontal lobe injury in humans

OBJECTIVE: To investigate whether frontal lobe damage in humans disrupts the natural tendency to preferentially attend to novel visual events in the environment. METHODS: Nine patients with chronic infarctions in the dorsolateral prefrontal cortex (DLPFC) and 23 matched normal controls participated in a study in which subjects viewed repetitive background stimuli, infrequent target stimuli, and novel visual stimuli (for example, fragmented or "impossible" objects). Subjects controlled viewing duration by a button press that led to the onset of the next stimulus. They also responded to targets by pressing a foot pedal. The amount of time spent looking at the different kinds of stimuli, and the target detection accuracy and speed served as dependent variables. RESULTS: Overall, normal controls spent significantly more time than frontal lobe patients looking at novel stimuli. Analysis of responses across blocks showed that initially frontal lobe patients behaved like normal controls by directing more attention to novel than background stimuli. However, they quickly began to distribute their viewing time evenly between novel and background stimuli, a pattern that was strikingly different from normal controls. By contrast, there were no differences between frontal lobe patients and normal controls for viewing duration devoted to background and target stimuli, target detection accuracy, or reaction time to targets. Frontal lobe patients did not differ from normal controls in terms of age, education, estimated IQ, or mood, but were more apathetic as measured by self report and informants' judgments. Attenuated responses to novel stimuli significantly correlated with degree of apathy. CONCLUSIONS: This study demonstrates that DLPFC injury selectively impairs the natural tendency to seek stimulation from novel and unusual stimuli. These data provide the first quantitative behavioural demonstration that the human frontal lobes play a critical part in directing and sustaining attention to novel events. The impairment of novelty seeking behaviour may contribute to the characteristic apathy found in patients with frontal lobe injury.     

Motor events underlying gastro-oesophageal reflux in ambulant patients with reflux oesophagitis

Abstract Information on the mechanism of gastro-oesophageal reflux in patients with reflux disease is limited largely to studies in resting recumbent subjects. Evidence exists that both posture and physical activity may influence reflux. The aim of this study was to investigate reflux mechanisms in ambulant patients with reflux oesophagitis. Concurrent ambulatory oesophageal manometry and pH monitoring were performed in 11 ambulant patients with erosive oesophagitis. Lower oesophageal sphincter (LOS) pressure was monitored with a perfused sleeve sensor. Recordings were made for 90 min before and 180 min after a meal. At set times patients sat in a chair or walked. LOS pressure was ≤2 mmHg at the time of reflux for 98% of reflux episodes. Transient LOS relaxation was the most common pattern overall and the predominant pattern in seven patients, whilst persistently absent basal LOS pressure was the most common pattern in four patients. The pattern of LOS pressure was not altered by the presence of hiatus hernia or by walking. Straining occurred at the onset of 31% of acid reflux episodes but often followed the development of an oesophageal common cavity. The occurrence of straining was not influenced by walking. In ambulant patients with reflux oesophagitis: (1) LOS pressure is almost always absent at the time of reflux, usually because of transient LOS relaxation, (2) persistently absent basal LOS pressure is an important mechanism of reflux in a few patients, (3) straining may help to induce acid reflux in a variable proportion of occasions and may in some instances be a response to gas reflux, and (4) walking does not influence the occurrence of reflux or its mechanisms.     

Frontal and parietal components of a cerebral network mediating voluntary attention to novel events

Despite the important role that attending to novel events plays in human behavior, there is limited information about the neuroanatomical underpinnings of this vital activity. This study investigated the relative contributions of the frontal and posterior parietal lobes to the differential processing of novel and target stimuli under an experimental condition in which subjects actively directed attention to novel events. Event-related potentials were recorded from well-matched frontal patients, parietal patients, and non-brain-injured subjects who controlled their viewing duration (by button press) of line drawings that included a frequent, repetitive background stimulus, an infrequent target stimulus, and infrequent, novel visual stimuli. Subjects also responded to target stimuli by pressing a foot pedal. Damage to the frontal cortex resulted in a much greater disruption of response to novel stimuli than to designated targets. Frontal patients exhibited a widely distributed, profound reduction of the novelty P3 response and a marked diminution of the viewing duration of novel events. In contrast, damage to posterior parietal lobes was associated with a substantial reduction of both target P3 and novelty P3 amplitude; however, there was less disruption of the processing of novel than of target stimuli. We conclude that two nodes of the neuroanatomical network for responding to and processing novelty are the prefrontal and posterior parietal regions, which participate in the voluntary allocation of attention to novel events. Injury to this network is indexed by reduced novelty P3 amplitude, which is tightly associated with diminished attention to novel stimuli. The prefrontal cortex may serve as the central node in determining the allocation of attentional resources to novel events, whereas the posterior parietal lobe may provide the neural substrate for the dynamic process of updating one's internal model of the environment to take into account a novel event.     

Orbitofrontal cortex biases attention to emotional events

We examined the role of orbitofrontal (OF) cortex in regulating emotion-attention interaction and the balance between involuntary and voluntary attention allocation. We studied patients with OF lesion applying reaction time (RT) and event-related potential (ERP) measures in a lateralized visual discrimination task with novel task-irrelevant affective pictures (unpleasant, pleasant, or neutral) preceding a neutral target. This allowed for comparing the effects of automatic attention allocation to emotional versus neutral stimuli on subsequent voluntary attention allocation to target stimuli. N2-P3a and N2-P3b ERP components served as measures of involuntary and voluntary attention allocation correspondingly. Enhanced N2-P3a amplitudes to emotional distractors and reduced N2-P3b amplitudes to targets preceded by emotional distractors were observed in healthy subjects, suggesting automatic emotional orienting interfered with subsequent voluntary orienting. OF patients showed an opposite pattern with tendency towards reduced N2-P3a responses to emotional distractors, suggesting impaired automatic orienting to emotional stimuli due to orbitofrontal damage. Enhanced N2-P3b responses to targets preceded by any affective distractor were observed in OF patients, suggesting bias towards voluntary target-related attention allocation due to orbitofrontal lesion. Behavioral evidence indicated that left visual field (LVF) attention performance was modulated by emotional stimuli. Specifically, OF patients responded faster to LVF targets subsequent to pleasant emotional distractors. We suggest that damage to the orbitofrontal circuitry leads to dysbalance between voluntary and involuntary attention allocation in the context of affective distractors with predisposition to posterior target-related processing over frontal novelty and affect-related processing. Furthermore, we suggest that orbitofrontal influence on emotion-attention interaction is valence and hemisphere dependent.     

Psychophysiological mechanisms underlying spatial attention in children with primary headache

Objective

Neurophysiological studies to evaluate spatial attention in children with primary headache are lacking. Tactile spatial attention modulates the N140 somatosensory evoked potential (SEP) amplitude.The aims of the study are: (1) to investigate the effect of spatial attention on the N140 amplitude in children with migraine and tension-type headache (TTH) and in healthy children, and (2) to correlate the neurophysiological results with a neuropsychological test for spatial attention.

Methods

We studied 16 patients with migraine without aura (MoA), 12 TTH children and 10 healthy subjects. “Deux Barrage” test for spatial attention was administered. SEPs were recorded in a neutral condition (NC) and in a spatial attention condition (SAC).

Results

No significant differences in neuropsychological measures were found between MoA, TTH and healthy subjects. The N140 amplitude increase during SAC, as compared to NC, was significantly higher in patients than in healthy controls. Migraineurs showed a positive correlation between the N140 amplitude increase during SAC and their neuropsychological performance.

Conclusions

Although spatial attention performances in children with headache are as good as in controls, the N140 amplitude increase during SAC in headache patients suggests that the psychophysiological mechanisms subtending spatial attention are different from those in healthy children.     

Visuotopic cortical connectivity underlying attention revealed with white-matter tractography

Visual attention selects behaviorally relevant information for detailed processing by resolving competition for representation among stimuli in retinotopically organized visual cortex. The signals that control this attentional biasing are thought to arise in a frontoparietal network of several brain regions, including posterior parietal cortex. Recent studies have revealed a topographic organization in the intraparietal sulcus (IPS) that mirrors the retinotopic organization in visual cortex, suggesting that connectivity between these regions might provide the mechanism by which attention acts on early cortical representations. Using white-matter imaging and functional MRI, we examined the connectivity between two topographic regions of IPS and six retinotopically defined areas in visual cortex. We observed a strong positive correlation between attention modulations in visual cortex and connectivity of posterior IPS, suggesting that these white-matter connections mediate the attention signals that resolve competition among stimuli for representation in visual cortex. Furthermore, we found that connectivity between IPS and V1 consistently respects visuotopic boundaries, whereas connections to V2 and V3/VP disperse by 60%. This pattern is consistent with changes in receptive field size across regions and suggests that a primary role of posterior IPS is to code spatially specific visual information. In summary, we have identified white-matter pathways that are ideally suited to carry attentional biasing signals in visuotopic coordinates from parietal control regions to sensory regions in humans. These results provide critical evidence for the biased competition theory of attention and specify neurobiological constraints on the functional brain organization of visual attention.     

Distinct brain dysfunctions underlying visuo-constructive deficit in DLB and AD

Brain Imaging and Behavior - Visuo-constructive abilities are a multicomponential process that can be impaired in several neurodegenerative dementias. Among visuo-constructive tasks, the...     

Prevalence of traumatic early life events in 31 agoraphobic patients with panic attacks

The rate of traumatic early life events in 31 agoraphobic subjects with panic attacks was significantly higher than that in matched control subjects. Experience of maternal separation, parental divorce, and events occurring after the age of 4 years was significantly more common.     

Differential neural mechanisms underlying exogenous attention to peripheral and central distracters

Mechanisms underlying exogenous attention to central and peripheral distracters were temporally and spatially explored while 30 participants performed a digit categorization task. Neural (event-related potentials—ERPs-, analyzed both at the scalp and at the voxel level) and behavioral indices of exogenous attention were analyzed. Distracters were either biologically salient or neutral, in order to test whether the exogenous attention bias to the former observed in previous studies is independent of, or interacts with, distracter eccentricity. Two subcomponents of the N2 component of the ERPs, N2olp and N2ft, reflected processes related to peripheral distracters processing. N2olp effects, located in the dorsal attention network (supplementary motor area), were probably related to covert reorientation to peripheral distracters. N2ft effects, located in the default mode network (posterior cingulate cortex), appeared to reflect less effort in the ongoing task when peripheral distracters were presented. N2ft also showed a biological saliency effect which was independent of eccentricity and was located in the polar/ventral prefrontal cortex. P3 showed greater amplitudes to centrally presented distracters. These latter effects were located in TEO (visual cortex), and would be functionally associated with spatial interference between the target and central distracters. Behavior showed the relevance of both central and peripheral distracters in exogenous attention. These results indicate that exogenous attention to peripheral distracters differed in temporal and spatial terms from exogenous attention to central distracters and that it is biased towards biologically salient events irrespective of their eccentricity.     

Impairment in dating and retrieving remote events in patients with early Parkinson''s disease.

Remote memory has been studied in a group of 25 non-demented patients with Parkinson's disease and their performance has been compared with that of 22 healthy control subjects. Only patients who scored > or = 27 on the mini mental state examination and with no anticholinergic treatment were included in the sample. A remote memory questionnaire was given, to evaluate memory for public events that occurred from 1966 to 1990. Each event was probed with five questions concerning its content and one for the date. Compared with healthy subjects, patients with Parkinson's disease were significantly impaired both in recalling the content and in dating remote events. These results support the claim that remote memory in patients with Parkinson's disease is disrupted independently of dementia. This impairment might result from a dysfunction at the level of the circuit connecting the basal ganglia to the frontal lobes.     

Right fronto-parietal dysfunction underlying spatial attention in bipolar disorder

Although the neural underpinning of bipolar disorder (BD) is still unknown, recent research suggests that the right fronto-parietal cortex is particularly affected in BD patients. If this were true, we would expect atypical functional cerebral asymmetries in allocation of visuospatial attention. To test this hypothesis, euthymic BD patients and age- and gender-matched healthy controls were compared on the visual line-bisection task, a reliable measure of visuospatial attention, associated with right parietal function. Line bisection performance (i.e. absolute and directional bias) was compared between groups as a function of response hand and line position. The results showed a typical hand-use effect in healthy controls involving a larger leftward bias (i.e. pseudoneglect) with the left hand than with the right hand. Although euthymic BD patients did not differ from healthy controls in the overall accuracy (i.e. absolute bias), they differed significantly in the directional line bisection bias. In contrast to healthy controls, BD patients did not significantly deviate from the veridical center, regardless of which hand was used to bisect horizontal lines. This finding indicates an atypical functional cerebral asymmetry in visuospatial attention in euthymic BD patients, supporting the idea of a dysfunction especially in the right fronto-parietal cortex.     

Deficits of the cholinergic system in early AD

Impairment of cholinergic neurotransmission is a well-established fact in Alzheimer's disease (AD) but there is controversy about its relevance at the early stages of the disease. In the recent years new techniques for in vivo imaging of key components of the cholinergic system in humans have developed. They are beginning to be applied to the very early stages of AD. Preliminary results suggest that there is early impairment of presynaptic receptors and acetylcholine esterase, the main degrading enzyme for acetylcholine, in cerebral cortex. The relation of these findings to neuronal function and post-mortem findings is being discussed.     

Delay in referral of patients with ruptured aneurysms to neurosurgical attention

Aneurysmal subarachnoid hemorrhage is a neurosurgical emergency. Early medical intervention is axiomatic for minimizing rebleeding and ischemia from vasospasm and achieving optimum results. The purpose of this study was to document the length and causes of the delay in referral which occur in patients following aneurysmal subarachnoid hemorrhage. The case histories of 150 consecutive patients admitted to The University of Iowa with proven ruptured aneurysms were studied. Medical records from The University of Iowa and referring hospitals were reviewed, and patients, families, and referring physicians interviewed. Overall, only 36% were referred within 48 hours of their first clear cut, recognizable sign or symptom of subarachnoid hemorrhage. Median time to referral was 3.6 days. Delay was due to physician diagnostic problems in 37%, delayed referral policy in 23%, unstable patient condition in 7%, failure of patients to recognize severity of illness in 8%, and logistical reasons in 12%. These data suggest that a large proportion of patients have a delay in achieving definitive neurosurgical care following aneurysm rupture, and that for the most part this delay is avoidable. More emphasis must be placed on public health and primary physician education regarding subarachnoid hemorrhage.     

The contribution of early traumatic events to schizophrenia in some patients: a traumagenic neurodevelopmental model

The current diathesis-stress model of schizophrenia proposes that a genetic deficit creates a predisposing vulnerability in the form of oversenstivity to stress. This model positions all psychosocial events on the stress side of the diathesis-stress equation. As an example of hypotheses that emerge when consideration is given to repositioning adverse life events as potential contributors to the diathesis, this article examines one possible explanation for the high prevalence of child abuse found in adults diagnosed schizophrenic. A traumagenic neurodevelopmental (TN) model of schizophrenia is presented, documenting the similarities between the effects of traumatic events on the developing brain and the biological abnormalities found in persons diagnosed with schizophrenia, including overreactivity of the hypothalamic-pituitary-adrenal (HPA) axis; dopamine, norepinephrine, and serotonin abnormalities; and structural changes to the brain such as hippocampal damage, cerebral atrophy, ventricular enlargement, and reversed cerebral asymmetry. The TN model offers potential explanations for other findings in schizophrenia research beyond oversensitivity to stress, including cognitive impairment, pathways to positive and negative symptoms, and the relationship between psychotic and dissociative symptomatology. It is recommended that clinicians and researchers explore the presence of early adverse life events in adults with psychotic symptoms in order to ensure comprehensive formulations and appropriate treatment plans, and to further investigate the hypotheses generated by the TN model.     

Neuropathology underlying clinical variability in patients with synucleinopathies

Abnormal aggregates of the synaptic protein, α-synuclein, are the dominant pathology in syndromes known as the synucleinopathies. The cellular aggregation of the protein occurs in three distinct types of inclusions in three main clinical syndromes. α-Synuclein deposits in neuronal Lewy bodies and Lewy neurites in idiopathic Parkinson’s disease (PD) and dementia with Lewy bodies (DLB), as well as incidentally in a number of other conditions. In contrast, α-synuclein deposits largely in oligodendroglial cytoplasmic inclusions in multiple system atrophy (MSA). Lastly, α-synuclein also deposits in large axonal spheroids in a number of rarer neuroaxonal dystrophies. Disorders are usually defined by their most dominant pathology, but for the synucleinopathies, clinical heterogeneity within the main syndromes is well documented. MSA was originally viewed as three different clinical phenotypes due to different anatomical localization of the lesions. In PD, recent meta-analyses have identified four main clinical phenotypes, and clinicopathological correlations suggest that more severe and more rapid progression of pathology with chronological age, as well as the involvement of additional neuropathologies, differentiates these phenotypes. In DLB, recent large studies show that clinical diagnosis is too insensitive to identify the syndrome itself, although clinicopathological studies suggest variable clinical features occur in the different pathological forms of this syndrome (pure DLB, DLB with Alzheimer’s disease (AD), and AD with amygdala predominant Lewy pathology). The recognition of considerable heterogeneity within the synucleinopathy syndromes is important for the identification of factors involved in changing their pathological phenotype.     

重视重症肌无力的早期规范化诊断

重症肌无力(MG)虽然是一种难治之症,但却是可治之症。治疗越早效果越好,遗憾的是确有不少患者因长期误诊而延误治疗,许多患者由MG眼肌型转化为全身型,由轻度全身型发展成重度全身型、甚至MG危象。这不仅严重影响了患者的生活质量,甚至危及生命。故重视MG的早期规范化诊断非常必