One-trial perceptual learning in the absence of conscious remembering and independent of the medial temporal lobe

A degraded, black-and-white image of an object, which appears meaningless on first presentation, is easily identified after a single exposure to the original, intact image. This striking example of perceptual learning reflects a rapid (one-trial) change in performance, but the kind of learning that is involved is not known. We asked whether this learning depends on conscious (hippocampus-dependent) memory for the images that have been presented or on an unconscious (hippocampus-independent) change in the perception of images, independently of the ability to remember them. We tested five memory-impaired patients with hippocampal lesions or larger medial temporal lobe (MTL) lesions. In comparison to volunteers, the patients were fully intact at perceptual learning, and their improvement persisted without decrement from 1 d to more than 5 mo. Yet, the patients were impaired at remembering the test format and, even after 1 d, were impaired at remembering the images themselves. To compare perceptual learning and remembering directly, at 7 d after seeing degraded images and their solutions, patients and volunteers took either a naming test or a recognition memory test with these images. The patients improved as much as the volunteers at identifying the degraded images but were severely impaired at remembering them. Notably, the patient with the most severe memory impairment and the largest MTL lesions performed worse than the other patients on the memory tests but was the best at perceptual learning. The findings show that one-trial, long-lasting perceptual learning relies on hippocampus-independent (nondeclarative) memory, independent of any requirement to consciously remember.

A striking visual effect can be demonstrated by using a grayscale image of an object that has been degraded to a low-resolution, black-and-white image (1, 2). Such an image is difficult to identify (Fig. 1) but can be readily recognized after a single exposure to the original, intact image (Fig. 2) (3–6). Neuroimaging studies have found regions of the neocortex, including high-level visual areas and the medial parietal cortex, which exhibited a different pattern of activity when a degraded image was successfully identified (after seeing the intact image) than when the same degraded image was first presented and not identified (4, 5, 7). This phenomenon reflects a rapid change in performance based on experience, in this case one-trial learning, but the kind of learning that is involved is unclear.Open in a separate windowFig. 1.A sample degraded image. Most people cannot identify what is depicted. See Fig. 2.Open in a separate windowFig. 2.An intact version of the image in Fig. 1. When the intact version is presented just once directly after presentation of the degraded version, the ability to later identify the degraded image is greatly improved, even after many months. Reprinted from ref. (42), which is licensed under CC BY 4.0.One possibility is that successful identification of degraded images reflects conscious memory of having recently seen degraded images followed by their intact counterparts. When individuals see degraded images after seeing their “solutions,” they may remember what is represented in the images, at least for a time. In one study, performance declined sharply from 15 min to 1 d after the solutions were presented and then declined more gradually to a lower level after 21 d (3). Alternatively, the phenomenon might reflect a more automatic change in perception not under conscious control (8). Once the intact image is presented, the object in the degraded image may be perceived directly, independently of whether it is remembered as having been presented. By this account, successful identification of degraded images is reminiscent of the phenomenon of priming, whereby perceptual identification of words and objects is facilitated by single encounters with the same or related stimuli (9–11). Some forms of priming persist for quite a long time (weeks or months) (12–14).These two possibilities describe the distinction between declarative and nondeclarative memory (15, 16). Declarative memory affords the capacity for recollection of facts and events and depends on the integrity of the hippocampus and related medial temporal lobe structures (17, 18). Nondeclarative memory refers to a collection of unconscious memory abilities including skills, habits, and priming, which are expressed through performance rather than recollection and are supported by other brain systems (19–21). Does one-trial learning of degraded images reflect declarative or nondeclarative memory? How long does it last? In an early report that implies the operation of nondeclarative memory, two patients with traumatic amnesia improved the time needed to identify hidden images from 1 d to the next, but could not recognize which images they had seen (22). Yet, another amnesic patient reportedly failed such a task (23). The matter has not been studied in patients with medial temporal lobe (MTL) damage.To determine whether declarative (hippocampus-dependent) or nondeclarative (hippocampus-independent) memory supports the one-trial learning of degraded images, we tested five patients with bilateral hippocampal lesions or larger MTL lesions who have severely impaired declarative memory. The patients were fully intact at perceptual learning, and performance persisted undiminished from 1 d to more than 5 mo. At the same time, the patients were severely impaired at remembering both the structure of the test and the images themselves.     

Neuronal representations of distance in human auditory cortex

Neuronal mechanisms of auditory distance perception are poorly understood, largely because contributions of intensity and distance processing are difficult to differentiate. Typically, the received intensity increases when sound sources approach us. However, we can also distinguish between soft-but-nearby and loud-but-distant sounds, indicating that distance processing can also be based on intensity-independent cues. Here, we combined behavioral experiments, fMRI measurements, and computational analyses to identify the neural representation of distance independent of intensity. In a virtual reverberant environment, we simulated sound sources at varying distances (15-100 cm) along the right-side interaural axis. Our acoustic analysis suggested that, of the individual intensity-independent depth cues available for these stimuli, direct-to-reverberant ratio (D/R) is more reliable and robust than interaural level difference (ILD). However, on the basis of our behavioral results, subjects' discrimination performance was more consistent with complex intensity-independent distance representations, combining both available cues, than with representations on the basis of either D/R or ILD individually. fMRI activations to sounds varying in distance (containing all cues, including intensity), compared with activations to sounds varying in intensity only, were significantly increased in the planum temporale and posterior superior temporal gyrus contralateral to the direction of stimulation. This fMRI result suggests that neurons in posterior nonprimary auditory cortices, in or near the areas processing other auditory spatial features, are sensitive to intensity-independent sound properties relevant for auditory distance perception.     

Medial temporal lobe atrophy in vascular dementia: visual temporal lobe rating scale

Medial temporal lobe atrophy (MTA) as assessed by magnetic resonance imaging (MRI) can be measured in several ways. First of all, visual rating scale is a quick and easy measurement. MTA is a sensitive marker for Alzheimer's disease (AD), but not specific. It has been documented in other dementias including vascular dementia (VD). This study is to evaluate the degree of MTA in VD patients using a standardized visual rating scale and to suggest the importance of the possible role of MTA in VD. Twenty-five VD, 33 AD and 27 non-demented patients underwent a coronal three-dimensional magnetization prepared rapid gradient echo brain MRI sequence. MTA was rated visually using a 5-point rating scale from 0 (no atrophy) to 4 (severe atrophy). The mean summed MTA score was 5.39 in AD, 2.16 in VD and 0.56 in non-demented patients. Most of the VD patients (80%) showed MTA. They were greater in bilateral sides compared with the non-demented group, but milder than in AD. Additionally, MTA of left side score was significantly associated with age. Medial temporal lobe volumes measured visually are smaller in size in patients with VD, although not to the same extent as in AD. This suggests that MTA in VD patients may be associated with pre-existing AD.     

Oscillatory patterns in temporal lobe reveal context reinstatement during memory search

Psychological theories of memory posit that when people recall a past event, they not only recover the features of the event itself, but also recover information associated with other events that occurred nearby in time. The events surrounding a target event, and the thoughts they evoke, may be considered to represent a context for the target event, helping to distinguish that event from similar events experienced at different times. The ability to reinstate this contextual information during memory search has been considered a hallmark of episodic, or event-based, memory. We sought to determine whether context reinstatement may be observed in electrical signals recorded from the human brain during episodic recall. Analyzing electrocorticographic recordings taken as 69 neurosurgical patients studied and recalled lists of words, we uncovered a neural signature of context reinstatement. Upon recalling a studied item, we found that the recorded patterns of brain activity were not only similar to the patterns observed when the item was studied, but were also similar to the patterns observed during study of neighboring list items, with similarity decreasing reliably with positional distance. The degree to which individual patients displayed this neural signature of context reinstatement was correlated with their tendency to recall neighboring list items successively. These effects were particularly strong in temporal lobe recordings. Our findings show that recalling a past event evokes a neural signature of the temporal context in which the event occurred, thus pointing to a neural basis for episodic memory.     

Complete atrioventricular block during temporal lobe epilepsy. Apropos of a case

The authors report the case of a 37 years old woman with no previous medical history, admitted to hospital for investigation of unexplained syncope, sometimes associated with generalised fits. After standard non-invasive cardiovascular investigations, no diagnosis could be made. The tilt test induced a minor syncopal episode without reproducing the clinical symptoms. In view of the discordance between the induced and spontaneous symptoms, a neurological opinion was requested. During the recording of an electroencephalogram, syncopal atrioventricular block was observed, preceded by auditory hallucinations, reproducing exactly the clinical symptoms. Analysis of the sequence of events showed the conduction defect to arise after the onset of the epileptic fit, indicating a diagnosis of syncopal complete atrioventricular block complicating cryptogenic temporal epilepsy, and requiring specific treatment. This case illustrates the importance of close collaboration between cardiologists and neurologists in the management of cases of unexplained syncope.     

颞叶癫痫大鼠学习记忆障碍与海马区PSD-95表达的关系

目的研究颞叶癫痫大鼠在Morris水迷宫中学习、记忆能力与大鼠海马区PSD-95表达变化的关系。方法随机将40只W istar大鼠分为海人酸（KA）组（28只）和对照组（12只）。KA组采用KA腹腔注射制作颞叶癫痫大鼠模型,根据是否出现自发性再发作（SRS）分SRS组（A组）、无SRS组（B组）;对照组（C组）注射生理盐水。通过Morris水迷宫测验观察各组大鼠注射KA或生理盐水2、6周时的空间学习、记忆能力,采用HE染色观察大鼠海马的组织病理学变化,免疫组化法检测大鼠海马CA1、CA3区PSD-95的表达。结果A组大鼠注射KA或生理盐水6周时海马区未见广泛神经元丢失及胶质增生,偶见局部神经元丢失及胶质增生;B、C组大鼠未见神经元丢失及胶质增生。与A组2周时及B、C组在2、6周时相比,A组6周时的学习、记忆能力明显下降（P〈0.01）,相应海马CA1、CA3区PSD-95表达均明显降低（P〈0.05）。结论颞叶癫痫长期反复发作时海马区PSD-95表达的减少,可能是导致颞叶癫痫大鼠学习、记忆障碍的机制之一。     

老年人放射性脑损伤的动态磁共振波谱研究

目的 探讨老年人放射性脑损伤的代谢特点.方法 对15例接受放射治疗(放疗)老年鼻咽癌患者(老年组)在治疗前和接受放射线剂量为20 Gy、40 Gy、60 Gy时分别进行磁共振波谱检查,观察不同剂量时双侧颞叶主要代谢物比值的变化趋势;选择23例同期接受放疗的青年鼻咽癌患者为对照组.结果 放疗前,老年组N-乙酰天门冬氨酸(NAA)与肌酐(Cr)的比值(NAA/Cr)为1.86±0.17,胆碱(Cho)与Cr的比值(Cho/Cr)为1.84±0.23,分别高于和低于对照组(2.15±0.22、1.62±0.31,P＞0.05);放疗过程中,两组均表现为NAA峰和Cho峰降低,放射线剂量达20 Gy前NAA/Cr、Cho/Cr和NAA和Cho比值(NAA/Cho)降幅较小,放射线剂量20～60 Gy阶段降幅加快;放疗结束时,老年组Cho/Cr降低幅度小于对照组(P＜0.05),NAA/Cr降低的幅度大于对照组,差异有统计学意义(P＜0.01).结论 接受边缘放射线辐射条件下,老年人放射性脑损伤发生较早,神经元损伤程度大于青年人,而对胶质细胞损伤程度相对较小.

Abstract：

Objective To study the metabolic characteristics of temporal lobe injury during the radiotherapy in the elderly with nasopharyngeal carcinoma through 1H- magnetic resonance spectroscopy (MRS). Methods The 15 aged and 23 young cases among 80 cases with nasopharyngeal carcinoma confirmed clinically and receiving radiotherapy for the first time were involved in the same period of July 2006 to May 2009. Conventional MRI scanning and bilateral temporal MRS were performed before and during radiotherapy at radiation dosages of 20 Gy, 40 Gy, and 60 Gy respectively. The spectroscopy morphology and the ratios of the three main metabolites were compared and analyzed. Results The values of N-acetylasparate (NAA)/creatine (Cr) was lower and choline-containing compound (Cho)/Cr ratio was higher in aged group than in young group before radiotherapy (P＞0.05). The spectroscopy morphology stepped down, NAA, Cho, NAA/Cr, Cho/Cr and NAA/Cho decreased to some extent along with the adding of radiation dosages in the course of radiotherapy. At the end of radiotherapy, the decreased amplitude of NAA/Cr value was larger in aged group than in control group (P＜0.01), and the amplitude of Cho/Cr value was lower than other group. Conclusions The neurons of aged patients with nasopharyngeal carcinoma have a weak tolerance to the radiation, brain injury occurs earlier and heavier in aged patients than in young patients. It is necessary to prevent neuron injury early.     

颞叶癫痫大鼠学习记忆障碍与海马病理变化的相关性研究

目的 探讨大鼠颞叶癫痫发作后不同时问学习、记忆障碍程度与海马病理变化的相关性。方法 采用立体定向技术在大鼠右侧海马注射红藻氨酸诱发颡叶癫痫发作,观察其行为学表现、脑电图变化,Morris水迷宫评价不同时间段学习、记忆障碍程度,以及海马、皮质病理变化。结果 注射红藻氨酸大鼠出现颞叶癫痫发作,随发作时间延长出现不同程度学习、记忆障碍,定位航行实验示逃避潜伏期延长,空间搜索实验示原平台象限内游泳时问百分比下降,与对照组比较均有显著性差异（P〈0．05）,发作后2个月达到高峰。右侧海马锥体细胞逐渐出现变性、坏死,由CA3区向CA4、CA2、CA1区扩展,2个月达到高峰;对侧海马锥体细胞也出现变性、坏死。但程度明显低于注射侧。结论 大鼠颡叶癫痫发作后,其学习、记忆障碍程度与海马变性、坏死程度具有一定相关性。     

Individual differences in neurocognitive aging of the medial temporal lobe

A wide spectrum of outcomes in the cognitive effects of aging is routinely observed in studies of the elderly. Individual differences in neurocognitive aging are also a characteristic of other species, such as rodents and non-human primates. In particular, investigations at behavioral, brain systems, cellular and molecular levels of analysis have provided much information on the basis for individual differences in neurocognitive aging among healthy outbred rats. These findings are likely to be relevant to an understanding of the effects of aging on the brain, apart from neurodegenerative conditions, such as Alzheimer’s disease, which do not naturally occur in rodents. Here we review and integrate those findings in a model supporting the concept that certain features of cognitive decline are caused by distributed alterations in the medial temporal lobe, which alter the information processing functions of the hippocampal formation. An additional emerging concept from this research is that preserved abilities at older ages may depend on adaptive changes in the hippocampal system that distinguish successful aging.     

Hyperprolactinemia and temporal lobe epilepsy in a woman: concomitant and persistent prolactin suppression and temporal lobe epilepsy relief

It has been reported that hyperprolactinemia may be associated with increased temporal lobe activity. Coexisting hyperprolactinemia (97.5 +/- 3.2 ng/ml) related to a pituitary tumefaction (8 mm) and Temporal Lobe Epilepsy (TLE), were observed in a 37-year-old woman. Carbamazepin (CBZ) therapy induced a marked improvement in TLE symptoms and EEG recordings, but did not influence hyperprolactinemia and related symptoms. Long-lasting (27 months) normoprolactinemia (19.4 +/- 0.6 ng/ml) and TLE relief were achieved on a dopamine (DA) agonist medication, e.g. pergolide mesylate, 25-50 micrograms/day given over 8 months, and persisted as long as 27 months after drug withdrawal. Posttreatment CT scans showed progressive shrinkage of the pituitary tumor (2 mm) associated with an empty-sella. It is proposed that, whenever TLE and hyperprolactinemia coexist, therapy with a DA agonist such as pergolide mesylate, resulting in normoprolactinemia, may be beneficial in TLE control.     

Clinical characteristics of nonlesional temporal lobe epilepsy

正Objective To investigate the clinical characteristics,memory and neuroimaging features of nonlesional tempo-ral lobe epilepsy (TLE-NL).Methods Forty-four patients with TLE-NL and 53 patients with unilateral temporal lobe epilepsy with hippocampal sclerosis (TLEHS) were recruited from the Second Affiliated Hospital of Zhejiang University from September 1st 2012 to August 31st 2017.The clinical characteristics were systematically analyzed and compared between TLE-NL and TLE-HS.Twenty healthy volunteers were also recruited.Memory     

Single-neuron correlates of subjective vision in the human medial temporal lobe

Visual information from the environment is transformed into perceptual sensations through several stages of neuronal processing. Flash suppression constitutes a striking example in which the same retinal input can give rise to two different conscious visual percepts. We directly recorded the responses of individual neurons during flash suppression in the human amygdala, entorhinal cortex, hippocampus, and parahippocampal gyrus, allowing us to explore the neuronal responses in untrained subjects at a high spatial and temporal resolution in the medial temporal lobe. Subjects were patients with pharmacologically intractable epilepsy implanted with depth electrodes to localize the seizure onset focus. We observed that the activity of two thirds of all visually selective neurons followed the perceptual alternations rather than the retinal input. None of the selective neurons responded to a perceptually suppressed stimulus. Therefore, the activity of most individual neurons in the medial temporal lobe of naive human subjects directly correlates with the phenomenal visual experience.     

Attentional integration between anatomically distinct stimulus representations in early visual cortex

Vision often requires attending to, and integrating information from, distant parts of the visual field. However, the neural basis for such long-range integration is not clearly understood. Here, we demonstrate a specific neural signature of attentional integration between stimuli in different parts of the visual field. Using functional MRI, we found that a task requiring the integration of information between two attended but spatially separated stimuli actively modulated the degree of functional integration (in terms of effective connectivity) between their retinotopic representations in visual cortical areas V1, V2, and V4. Spatial attention enhanced long-distance coupling between distinct neuronal populations that represented the attended visual stimuli, even at the earliest stages of cortical processing. In contrast, unattended stimulus representations were decoupled both from attended representations and particularly strongly from each other. Furthermore, enhanced functional integration between cortical representations was associated with enhanced behavioral performance. Attention may thus serve to "bind" together cortical loci at multiple levels of the visual hierarchy that are commonly involved in processing attended stimuli, promoting integration between otherwise functionally isolated cortical loci.     

Insulin affects the neuronal response in the medial temporal lobe in humans

In recent years, clear evidence has accumulated that insulin affects central nervous functions. Besides controlling metabolic processes such as energy homeostasis by the regulation of food intake through hypothalamic receptors, the peptide hormone also appears to be capable of modulating cognitive functions. Experimental and clinical evidence for insulin supports effects on learning and memory. This study explores the impact of insulin on neuronal activity using a picture encoding task in a functional magnetic resonance imaging approach. Ten subjects performed two independent scanning sessions, each session divided into one part of four baseline runs and a second part of four runs during either insulin or saline was infused. A hyperinsulinemic- euglycemic clamp technique was applied to keep the blood glucose concentrations normal during insulin infusion. Contrast images between the two parts revealed identical activation patterns during baseline and saline conditions while during the insulin condition a higher level of activation was detected within the fusiform gyrus in both hemispheres. Shorter reaction times during the insulin condition underlined the cognitive benefit. For the first time, we were able to demonstrate that insulin enhances neuronal activity within the medio-temporal lobe and increased performance in humans under in-vivo conditions.     

Invariant representations of visual patterns in a temporal population code

Mammalian visual systems are characterized by their ability to recognize stimuli invariant to various transformations. Here, we investigate the hypothesis that this ability is achieved by the temporal encoding of visual stimuli. By using a model of a cortical network, we show that this encoding is invariant to several transformations and robust with respect to stimulus variability. Furthermore, we show that the proposed model provides a rapid encoding, in accordance with recent physiological results. Taking into account properties of primary visual cortex, the application of the encoding scheme to an enhanced network demonstrates favorable scaling and high performance in a task humans excel at.     

Characterization of aromatase cytochrome P450 activity in the human temporal lobe.

Local aromatase-mediated conversion of androgens plays an important role in androgen action on the brain. To characterize estrogen formation in the human brain, we measured the microsomal aromatase activity of temporal lobe biopsies and compared it to that of human placenta using a highly sensitive 3H2O assay with [1beta-3H]androstenedione as substrate. Brain tissue was removed neurosurgically from 23 patients with epilepsy. Data of kinetic studies were analyzed with a computer-assisted, nonlinear, curve-fitting method using the Michaelis-Menten plus a nonspecific metabolism model. In contrast to data for placental aromatase activity, that for brain always had to be corrected for nonspecific tritium release. The mean K, values were 22.2 nmol/L in brain and 49.6 nmol/L in placenta. Inhibition experiments with atamestane, an inhibitor of aromatase cytochrome P450, revealed specific, dose-responsive, and competitive inhibition of both brain and placental aromatase activities. Placental aromatase activity was completely suppressible by atamestane, whereas in brain tissue there remained a residue of nonspecific tritium release. Subsequent experiments with cerebral cortex and subcortical white matter specimens of children and adults revealed a significantly higher aromatase activity in cerebral cortex than in subcortical white matter, but no sex or age differences were found.     

Temporal-insular spreading time in temporal lobe epilepsy as a predictor of seizure outcome after temporal lobectomy

Insular involvement in temporal lobe epilepsy (TLE) has gradually been recognized since the widespread use of stereoelectroencephalography (SEEG). However, the correlation between insular involvement and failed temporal lobe surgery remains unclear. In this study, we analyzed the surgical outcomes of TLE patients who underwent temporal and insular SEEG recordings and explored the predictors of failed anterior temporal lobectomy (ATL) in these patients with temporal seizures.Forty-one patients who underwent ATL for drug-resistant TLE were examined using temporal and insular SEEG recordings. The clinical characteristics, SEEG data, and postoperative seizure outcomes of these patients were analyzed, and multivariate analysis was used to identify the predictors of surgical outcome.In this series, the ictal temporal discharges invaded the insula in 39 (95.1%) patients. Twenty-three (56.1%) patients were seizure-free (Engel class I) after ATL with at least 1 year follow-up. Only temporal-insular spreading time (TIST) was an independent predictor of postoperative seizure-free outcomes (P = .035). By creating receiver operating characteristic curves for TIST, 400 milliseconds was identified as the cutoff for classification. All patients were classified into 2 groups (TIST ≤ 400 milliseconds and TIST > 400 milliseconds) based on the cutoff value; the difference in seizure-free rates between the 2 groups was significant (P = .001).The very early insular involvement in TLE may be associated with poorer seizure outcomes after ATL. Our findings may be helpful for estimating the appropriate operative procedures and will be valuable for evaluating the prognosis of TLE patients with temporal-insular SEEG recordings and temporal lobectomy.     

Thyroid hormones, dementia, and atrophy of the medial temporal lobe

CONTEXT: Thyroid function has been related to Alzheimer disease (AD), but it remains unclear whether thyroid dysfunction results from or contributes to developing AD. OBJECTIVE: The objective of the study was to determine the association between thyroid function and both medial temporal lobe atrophy on brain magnetic resonance imaging (MRI) as putative early sign of AD and risk of dementia. DESIGN AND PARTICIPANTS: This was a population-based cohort study among 1077 elderly subjects aged 60-90 yr and dementia free at baseline (1995-1996). MAIN OUTCOME MEASURES: Nonfasting serum levels of TSH, free T(4) (fT(4)), T(3), and rT(3) were available in 1025 subjects followed up for incident dementia until 2005. In a subset of 489 nondemented elderly, we assessed volumes of the hippocampus and amygdala on brain MRI. Subjects using thyroid medication were excluded. RESULTS: During 5657 person-years of follow-up (mean 5.5 yr), 63 subjects were diagnosed with dementia (46 with AD). TSH and thyroid hormones were not associated with risk of dementia or AD. TSH and T(3) were also not related to brain atrophy, whereas nondemented subjects with higher fT(4) levels had more hippocampal and amygdalar atrophy on MRI. Similar associations were found for rT(3). Excluding subjects with thyroid disorders or incipient AD did not change the results. CONCLUSION: In our study, TSH was related neither to risk of AD nor with early MRI markers thereof, arguing against an important role of thyroid function in the development of AD. Whether the association of higher fT(4) and rT(3) levels with brain atrophy on MRI has functional significance remains to be elucidated.