Impaired frontostriatal cognitive functioning following posteroventral pallidotomy in advanced Parkinson's disease

We investigated the long-term effects of posteroventral pallidotomy on tests sensitive to the functional integrity of frontostriatal neural systems in a sample of 11 patients with advanced Parkinson's disease (PD). Patients were assessed within 1 month prior to surgery and at 12 months following pallidotomy. Changes in outcome measures were compared to a control sample of equally performing PD patients receiving nonsurgical medical management assessed over a 12-month period. Measures of cognitive abilities sensitive to frontostriatal functional integrity tested psychomotor processing speed, executive components of working memory, and reasoning. Additional tests of general mental status and semantic memory ability were utilized to assess the specificity of the effect of pallidotomy on cognitive function. Significant declines in performance on all measures sensitive to frontostriatal integrity were found for the surgery group but not the PD control group. No significant changes in performance were found on the measures of general mental status or semantic memory for either the surgery or PD control samples. These results suggest that the posteroventral pallidotomy selectively impairs performance on tests of frontostriatal cognitive abilities.     

Left posteroventral pallidotomy results in a deficit in verbal memory

Whilst pallidotomy is emerging as a popular approach to the treatment to Parkinson's disease, little is yet known about the cognitive effects of this procedure. This study presents 19 patients (6 right, 13 left) who were assessed both before and after the procedure on a battery of cognitive tests. The results indicate that subjects with left-sided lesions display significant decline in verbal memory between one and three months following the procedure. The results are consistent with the notion of either a classic amnesic syndrome or a deficit in striato-frontal working memory.     

The role of the human medial temporal lobe in object recognition and object discrimination.

This paper reviews evidence from neuropsychological patient studies relevant to two questions concerning the functions of the medial temporal lobe in humans. The first is whether the hippocampus and the adjacent perirhinal cortex make different contributions to memory. Data are discussed from two patients with adult-onset bilateral hippocampal damage who show a sparing of item recognition relative to recall and certain types of associative recognition. It is argued that these data are consistent with Aggleton and Brown's (1999) proposal that familiarity-based recognition memory is not dependent on the hippocampus but is mediated by the perirhinal cortex and dorso-medial thalamic nucleus. The second question is whether the recognition memory deficit observed in medial temporal lobe amnesia can be explained by a deficit in perceptual processing and representation of objects rather than a deficit in memory per se. The finding that amnesics were impaired at recognizing, after short delays, patterns that they could successfully discriminate suggests that their memory impairment did not result from an object-processing deficit. The possibility remains, however, that the human perirhinal cortex plays a role in object processing, as well as in recognition memory, and data are presented that support this possibility.     

The role of the human medial temporal lobe in object recognition and object discrimination

This paper reviews evidence from neuropsychological patient studies relevant to two questions concerning the functions of the medial temporal lobe in humans. The first is whether the hippocampus and the adjacent perirhinal cortex make different contributions to memory. Data are discussed from two patients with adult-onset bilateral hippocampal damage who show a sparing of item recognition relative to recall and certain types of associative recognition. It is argued that these data are consistent with Aggleton and Brown's (1999) proposal that familiarity-based recognition memory is not dependent on the hippocampus but is mediated by the perirhinal cortex and dorso-medial thalamic nucleus. The second question is whether the recognition memory deficit observed in medial temporal lobe amnesia can be explained by a deficit in perceptual processing and representation of objects rather than a deficit in memory per se. The finding that amnesics were impaired at recognizing, after short delays, patterns that they could successfully discriminate suggests that their memory impairment did not result from an object-processing deficit. The possibility remains, however, that the human perirhinal cortex plays a role in object processing, as well as in recognition memory, and data are presented that support this possibility.     

Different types of working memory binding in epilepsy patients with unilateral anterior temporal lobectomy

The medial temporal lobe is an important structure for long-term memory formation, but its role in working memory is less clear. Recent studies have shown hippocampal involvement during working memory tasks requiring binding of information. It is yet unclear whether this is limited to tasks containing spatial features. The present study contrasted three binding conditions and one single-item condition in patients with unilateral anterior temporal lobectomy.A group of 43 patients with temporal lobectomy (23 left; 20 right) and 20 matched controls were examined with a working memory task assessing spatial relational binding (object–location), non-spatial relational binding (object–object), conjunctive binding (object–colour) and working memory for single items. We varied the delay period (3 or 6 s), as there is evidence showing that delay length may modulate working memory performance.The results indicate that performance was worse for patients than for controls in both relational binding conditions, whereas patients were unimpaired in conjunctive binding. Single-item memory was found to be marginally impaired, due to a deficit on long-delay trials only.In conclusion, working memory binding deficits are found in patients with unilateral anterior temporal lobectomy. The role of the medial temporal lobe in working memory is not limited to tasks containing spatial features. Rather, it seems to be involved in relational binding, but not in conjunctive binding. The medial temporal lobe gets involved when working memory capacity does not suffice, for example when relations have to be maintained or when the delay period is long.     

工作记忆训练在精神疾病中的应用

随着工作记忆缺损与各类精神疾病的关联被逐渐阐明,研究者开始关注工作记忆训练能否作为干预手段应用在精神疾病领域中。当前,在对ADHD、精神分裂症、抑郁、焦虑、成瘾障碍和自闭症患者进行的工作记忆训练中发现了训练近迁移、远迁移以及临床症状缓解的相应证据,以及直接(通过提升工作记忆能力起效)和间接(通过提升其他关联能力起效)两条效益路径。此外,一个针对精神疾病患者的有效训练范式应当就三个层面进行考察:训练的一般成分(即受训的核心加工过程),训练的疾病特异成分(例如情绪工作记忆训练);以及训练的辅助性成分(例如动机、策略、慢波睡眠等)。未来研究需要关注适用不同精神疾病的训练范式与程序,促进工作记忆训练的定制化,并且通过完善评估手段进一步澄清工作记忆训练在病患中的效益机制。     

Does the body image exist in three dimensions? The study of visual mental representation of a body and a nonbody object

Do the mental images of 3-dimensional objects recreate the depth characteristics of the original objects? This investigation of the characteristics of mental images utilized a novel boundary-detection task that required participants to relate a pair of crosses to the boundary of an image mentally projected onto a computer screen. 48 female participants with body attitudes within expected normal range were asked to image their own body and a familiar object from the front and the side. When the visual mental image was derived purely from long-term memory, accuracy was better than chance for the front (64%) and side (63%) of the body and also for the front (55%) and side (68%) of the familiar nonbody object. This suggests that mental images containing depth and spatial information may be generated from information held in long-term memory. Pictorial exposure to views of the front or side of the objects was used to investigate the representations from which this 3-dimensional shape and size information is derived. The results are discussed in terms of three possible representational formats and argue that a front-view 2 1/2-dimensional representation mediates the transfer of information from long-term memory when depth information about the body is required.     

Dissociating mental transformations and visuo-spatial storage in working memory: evidence from representational neglect

A study is reported of visuo-spatial working memory in two individuals suffering from a cognitive deficit known as unilateral spatial neglect, and seven healthy control participants. Both patients have difficulties reporting details on the left side of imaged representations, and one has an additional difficulty with perceptual input to the left of his body midline. All participants were asked to report the location and identity of objects presented in novel 2 x 2 arrays that were either present throughout or were described orally by the experimenter, with no visual input. On half of the trials, the report was to be made from the opposite perspective, requiring 180 degree mental rotation of the mentally represented array. The patients show an impaired ability to report details from the presented or the imagined left, but had no difficulty with mental rotation. Results point to a clear separation between the processes of perception and those of visuo-spatial working memory. Results also suggest that the patients might be suffering from damage to the system used for holding visuo-spatial representations rather than a difficulty with attending to elements of that representation.     

Neuroanatomy and Neuropathology Associated with Korsakoff’s Syndrome

Although the neuropathology of Korsakoff's syndrome (KS) was first described well over a century ago and the characteristic brain pathology does not pose a diagnostic challenge to pathologists, there is still controversy over the neuroanatomical substrate of the distinctive memory impairment in these patients. Cohort studies of KS suggest a central role for the mammillary bodies and mediodorsal thalamus, and quantitative studies suggest additional damage to the anterior thalamus is required. Rare cases of KS caused by pathologies other than those of nutritional origin provide support for the role of the anterior thalamus and mammillary bodies. Taken together the evidence to date shows that damage to the thalamus and hypothalamus is required, in particular the anterior thalamic nucleus and the medial mammillary nucleus of the hypothalamus. As these nuclei form part of wider memory circuits, damage to the inter-connecting white matter tracts can also result in a similar deficit as direct damage to the nuclei. Although these nuclei and their connections appear to be the primary site of damage, input from other brain regions within the circuits, such as the frontal cortex and hippocampus, or more distant regions, including the cerebellum and amygdala, may have a modulatory role on memory function. Further studies to confirm the precise site(s) and extend of brain damage necessary for the memory impairment of KS are required.     

Dissociating mental transformations and visuo‐spatial storage in working memory: Evidence from representational neglect

A study is reported of visuo‐spatial working memory in two individuals suffering from a cognitive deficit known as unilateral spatial neglect, and seven healthy control participants. Both patients have difficulties reporting details on the left side of imaged representations, and one has an additional difficulty with perceptual input to the left of his body midline. All participants were asked to report the location and identity of objects presented in novel 2 × 2 arrays that were either present throughout or were described orally by the experimenter, with no visual input. On half of the trials, the report was to be made from the opposite perspective, requiring 180 degree mental rotation of the mentally represented array. The patients show an impaired ability to report details from the presented or the imagined left, but had no difficulty with mental rotation. Results point to a clear separation between the processes of perception and those of visuo‐spatial working memory. Results also suggest that the patients might be suffering from damage to the system used for holding visuo‐spatial representations rather than a difficulty with attending to elements of that representation.     

关联性记忆错觉神经机制的研究

该文介绍了近年来使用DRM范式对关联性记忆错觉神经机制的研究。脑损伤病人以及正常人的神经成像研究表明：对关键诱饵的虚假再认可能和对学过项目的正确再认有着相似而又不完全相同的脑机制;颞叶中部和额叶对关联性记忆错觉的产生十分重要,并且它们各自的作用似乎都不是单一的。     

Evidence for neocortical involvement in reference memory

Rats were trained on an eight-arm radial maze task using a procedure that provides for an assessment of both working and reference memory. Following training, rats received parietal cortex, medial prefrontal cortex, visual cortex, or nucleus basalis magnocellularis lesions. Rats with visual cortex lesions showed no change in performance on either working or reference memory. Rats with parietal cortex lesions displayed a temporary deficit in reference, but no deficit on working memory. Animals with medial prefrontal cortex lesions showed a temporary deficit on both working and reference memory. Rats with extensive lateral frontal and parietal cortex depletion of acetylcholinesterase following nucleus basalis magnocellularis lesions had a marked disruption only of reference but not of working memory. It is concluded that neocortex and possibly the cholinergic projections to neocortex play an important role in mediating reference memory.     

Disproportionate deficit in associative recognition relative to item recognition in global amnesia

In two experiments, we tested the hypothesis that medial temporal lobe (MTL) amnesic patients and, likewise, diencephalic (DNC) amnesic patients evidence a disproportionate deficit in memory for associations in comparison with memory for single items. In Experiment 1, we equated item recognition in amnesic and control participants and found that, under these conditions, associative recognition remained impaired both for MTL patients and for DNC patients. To rule out an alternative interpretation of the results of Experiment 1, in Experiment 2 we compared the performance of amnesic and control participants on a one-item recognition task and a two-item recognition task that required no memory for the association between members of word pairs. In the MTL group, when single-item recognition was equated to that of the controls, two-item nonassociative pair memory was equivalent as well. In the DNC group, nonassociative pair memory was impaired, but this impairment did not fully account for the impairment in associative memory. These findings indicate that memory for novel associations between items is disproportionately impaired in comparison with memory for single items in amnesia.     

Heterogeneity of auditory verbal working memory in schizophrenia

The heterogeneity of schizophrenia remains an obstacle for understanding its pathophysiology. Studies using a tone discrimination screening test to classify patients have found evidence for 2 subgroups having either a specific deficit in verbal working memory (WM) or deficits in both verbal and nonverbal memory. This study aimed to (a) replicate in larger samples differences between these subgroups in auditory verbal WM; (b) evaluate their performance on tests of explicit memory and sustained attention; (c) determine the relation of verbal WM deficits to auditory hallucinations and other symptoms; and (d) examine medication effects. The verbal WM and tone discrimination performance did not differ between medicated (n = 45) and unmedicated (n = 38) patients. Patients with schizophrenia who passed the tone screening test (discriminators; n = 60) were compared with those who did not (nondiscriminators; n = 23) and healthy controls (n = 47). The discriminator subgroup showed poorer verbal WM than did controls and a deficit in verbal but not visual memory on the Wechsler Memory Scale-Revised (Wechsler, 1987), whereas the nondiscriminator subgroup showed overall poorer performance on both verbal and nonverbal tests and a marked deficit in sustained attention. Verbal WM deficits in discriminators were correlated with auditory hallucinations but not with negative symptoms. The results are consistent with a verbal memory deficit in a subgroup of schizophrenia having intact auditory perception, which may stem from dysfunction of language-related cortical regions, and a more generalized cognitive deficit in a subgroup having auditory perceptual and attentional dysfunction.     

Short-Term Memory Deficits Are Not Uniform in Down and Williams Syndromes

Neuropsychological investigation of the development of the mnesic function in mental retardation has primarily focused on evaluating short-term memory (STM). Studies have often documented a reduced verbal short-term memory span in individuals with mental retardation and with Down syndrome in particular, compared to groups of mental age-matched controls. However, recent evidence suggests that verbal short-term memory is not equally impaired in all individuals with mental retardation. Findings in children with Williams syndrome are particularly relevant in this regard. Also, data concerning STM for visual information suggest that visual-object and visual-spatial working memory may be differently compromised in people with mental retardation. In particular, individuals with Williams syndrome exhibit specific difficulties in visual-spatial but not in visual-object working memory tasks compared to typically-developing children matched for mental age. Instead, people with Down syndrome show reduced performance in both visual-spatial and visual-object tests. Taken together, these results reinforce the view that intellectual disability is not a unitary condition characterized by homogeneous slowness of cognitive development but a variety of conditions in which some cognitive functions may be more disrupted than others. The finding that the working memory deficit in individuals with Williams and Down syndrome may be qualitatively differentiated also supports the hypothesis that it is not simply a manifestation of general cognitive impairment but, rather, the expression of a specific deficit of a discrete cognitive ability.     

Unilateral memory storage in the procerebrum of the terrestrial slug Limax

In most sensory modalities, neuronal inputs are bilaterally processed in a higher center. In some animal species, however, functional lateralization is sometimes observed in the sensory processing at the higher level. For the terrestrial slug Limax, olfaction is the most important sensory modality and this slug can acquire odor-aversion memories. Previously, it has been demonstrated in bilateral PC ablation experiments that the procerebrum (PC) is necessary for odor-aversion memory, and that the PC is the memory storage site. On the other hand, it has been hypothesized that only the unilateral PC is used for odor-aversion learning. Here we demonstrated that the number of the slugs with intact memory performance was reduced by approximately 50% when the PC was surgically ablated only unilaterally before or after conditioning. There was no difference in the memory performance of the right vs. the left PC-ablated slugs. However, memory deficit from unilateral PC ablation was not observed when the ipsilateral tentacles were also amputated at the same time. We also showed that there was no lateral memory transfer from one PC to the other, after up to 7 days post-conditioning. Our results demonstrated clearly that either the left or right PC is randomly used for olfactory learning, and that the side of use is determined at the level of the olfactory ascending pathway to the PC.     

A specific role for the human amygdala in olfactory memory

The medial temporal lobe is known to play a role in the processing of olfaction and memory. The specific contribution of the human amygdala to memory for odors has not been addressed, however. The role of this region in memory for odors was assessed in patients with unilateral amygdala damage due to temporal lobectomy (n = 20; 11 left, 9 right), one patient with selective bilateral amygdala damage, and in 20 age-matched normal controls. Fifteen odors were presented, followed 1 h later by an odor-name matching test and an odor-odor recognition test. Signal detection analyses showed that both unilateral groups were impaired in their memory for matching odors with names, these patients were not significantly impaired on odor-odor recognition. Bilateral amygdala damage resulted in severe impairment in both odor-name matching as well as in odor-odor recognition memory. Importantly, none of the patients were impaired on an auditory verbal learning task, suggesting that these findings reflect a specific impairment in olfactory memory, and not merely a more general memory deficit. Taken together, the data provide neuropsychological evidence that the human amygdala is essential for olfactory memory.     

Inferior Parietal Perfusion, Lateralization, and Neuropsychological Dysfunction in Alzheimer's Disease

The severity of inferior parietal perfusion deficits in Alzheimer's disease (AD) is strongly associated with global intellectual decline. The relationship to specific losses of neuropsychological functioning, however, is less clear, as is the relative importance of the side (left vs. right) of hemispheric deficit. In this study, 53 patients with probable AD and 35 elderly controls received both a resting¹³³Xe rCBF measurement and neuropsychological examination. AD patients demonstrated the expected bilateral deficits in inferior parietal perfusion, as well as impairment on measures of mental status, intelligence, verbal and visual memory, attention, language, and construction abilities. The severity of this bilateral parietal deficit, in turn, was associated with virtually all of these AD-related neuropsychological impairments, most strongly with declining Performance IQ. Left-sided deficits correlated better with overall declines in IQ, as well as with declining attention and language fluency. Right-sided deficits, on the other hand, correlated best with declines in mental status and—paradoxically—verbal memory and contributed independently to declines in Full Scale and Performance IQ. In terms of the number and strength of their association to neuropsychological measures, left-sided deficits appear much more predictive of cognitive decline in AD. Right-sided deficits, however, may be most important for predicting aspects of performance skill that are only indirectly assessed in standard paper-and-pencil format. Overall, it appears that both sides make significant, but independent contributions to general functional decline in AD, but that left-sided deficits are more closely associated with cognitive decline as measured by most standard neuropsychological measures.     

Memory for temporal order of new and familiar spatial location sequences: role of the medial prefrontal cortex

Rats with medial prefrontal cortex or sham control lesions were tested on an eight-arm radial maze task to examine memory for the temporal order of a variable and a constant sequence of spatial locations as a function of temporal distance. During the study phase of each trial, rats were allowed to visit each of eight arms once in an order that was randomly selected or fixed for that trial. The test phase required the rats to choose which of two arms occurred earlier in the sequence of arms visited during the study phase. The arms selected as test arms varied according to temporal distance (0, 2, 4, or 6) or the number of arms that occurred between the two test arms in the study phase. For the variable sequences based on new information, control rats showed an increasing temporal distance function. Relative to control rats, medial prefrontal cortex-lesioned rats displayed a temporal order memory deficit across all distances. For the constant sequence based on familiar information, control rats performed well across all distances. Relative to controls, the medial prefrontal cortex-lesioned rats displayed a performance deficit. The results support the idea that the medial prefrontal cortex contributes to mnemonic operations associated with temporal order for new and familiar spatial location information.