Verbal Encoding Deficits in a Patient with a Left Retrosplenial Lesion

Over the past decade, memory impairments associated with retrosplenial damage have received increased attention among neuroscientists, although the exact role of the retrosplenial region in memory has not been clearly defined. Evidence from lesion studies and functional neuroimaging has implicated the retrosplenial region in verbal episodic memory, temporal ordering of information, and topographical memory. In addition, recent positron emission tomography studies have shown increased activation of the retrosplenial cortex during tasks involving both the encoding and retrieval of episodic information. The objective of this study was to define more clearly the nature of memory impairments observed in retrosplenial amnesia. A 47-year-old amnesic male with a left retrosplenial arteriovenous malformation was examined on neurocognitive tasks of automatic and directed encoding, temporal ordering of information, and remote memory. Despite normal performance on frontal cognitive tasks, intact memory for remote information, and a superior IQ, this individual exhibited a profound deficit in the encoding of information, evidenced by poor release from proactive interference, poor category clustering on word list recall, poor semantic encoding on a levels of processing task, and mild impairments in temporal ordering. These results imply that the retrosplenial region plays a role in the verbal encoding of information, which contributes to the profound verbal memory impairment reported in previous case studies of patients with retrosplenial damage.     

Topographical,Autobiographical and Semantic Memory in a Patient with Bilateral Mesial Temporal and Retrosplenial Infarction

The relationship between clinical symptoms and neurocognitive impairment has been a growing interest in the field of schizophrenia research. We review the empirical evidence for whether some schizophrenia symptoms can be viewed as expressions of disordered executive functioning. A specific focus of our review is Frith’s (1992) neurocognitive theory of negative symptoms, and whether this theory is supported by studies of executive functioning in schizophrenia. The current trend towards viewing executive functioning in terms of fractionable cognitive processes is discussed. Difficulties with traditional clinical measures (e.g. the Wisconsin Card Sorting Test; WCST) in separating these processes are highlighted. Neurocognitive studies of schizophrenia are then reviewed in terms of this fractionated view of executive processes. We conclude that a more specific approach to executive functioning deficits in schizophrenia using more selective measures is needed before stronger conclusions can be drawn about their relationship to clinical symptoms.     

Verbal and Visual Memory Impairments in Bipolar I and II Disorder

Objective

To compare verbal and visual memory performances between patients with bipolar I disorder (BD I) and patients with bipolar II disorder (BD II) and to determine whether memory deficits were mediated by impaired organizational strategies.

Methods

Performances on the Korean-California Verbal Learning Test (K-CVLT) and the Rey-Osterrieth Complex Figure Test (ROCF) in 37 patients with BD I, 46 patients with BD II and 42 healthy subjects were compared. Mediating effects of impaired organization strategies on poor delayed recall was tested by comparing direct and mediated models using multiple regression analysis.

Results

Both patients groups recalled fewer words and figure components and showed lower Semantic Clustering compared to controls. Verbal memory impairment was partly mediated by difficulties in Semantic Clustering in both subtypes, whereas the mediating effect of Organization deficit on the visual memory impairment was present only in BD I. In all mediated models, group differences in delayed recall remained significant.

Conclusion

Our findings suggest that memory impairment may be one of the fundamental cognitive deficits in bipolar disorders and that executive dysfunctions can exert an additional influence on memory impairments.     

Antiretroviral Non-Adherence is Associated With a Retrieval Profile of Deficits in Verbal Episodic Memory

HIV-associated deficits in verbal episodic memory are commonly associated with antiretroviral non-adherence; however, the specific aspects of memory functioning (e.g., encoding, consolidation, or retrieval) that underlie this established relationship are not well understood. This study evaluated verbal memory profiles of 202 HIV+ participants who underwent a 30-day electronic monitoring of antiretroviral adherence. At the group level, non-adherence was significantly associated with lower scores on immediate and delayed passage recall and word list learning. Retention and recognition of passages and word lists were not related to adherence. Participants were then classified as having either a normal verbal memory profile, a “subcortical” retrieval profile (i.e., impaired free recall with relatively spared recognition), or a “cortical” encoding profile (e.g., cued recall intrusions) based on the Massman et al. (1990 Massman, P. J., Delis, D. C., Butters, N., Levin, B. E., & Salmon, D. P. (1990). Are all subcortical dementias alike? Verbal learning and memory in Parkinson’s and Huntington’s disease patients. Journal of Clinical and Experimental Neuropsychology, 12, 729–744. doi:10.1080/01688639008401015[Taylor & Francis Online], [Web of Science ®] , [Google Scholar]) algorithm for the California Verbal Learning Test. HIV+ participants with a classic retrieval deficit had significantly greater odds of being non-adherent than participants with a normal or encoding profile. These findings suggest that adherence to prescribed antiretroviral regimens may be particularly vulnerable to disruption in HIV+ individuals due to deficits in the complex process of efficiently accessing verbal episodic information with minimal cues. A stronger relationship between non-adherence and passage (vs. word list) recall was also found and may reflect the importance of contextual features in remembering to take medications. Targeted interventions for enhancing and supporting episodic memory retrieval processes may improve antiretroviral adherence and overall health outcomes among persons living with HIV.     

Verbal Learning and Memory Deficits in Traumatic Brain Injury: Encoding,Consolidation, and Retrieval

The present study examined the nature of verbal memory deficits in individuals with traumatic brain injury (TBI) compared to healthy controls. The study was designed to control for methodological shortcomings of previous related research. Three groups of participants were used: (a) a head injured sample with moderate to severe traumatic brain injuries (N=55), (b) a control sample matched on age and initial performance on CVLT Trial 5 and Sum of Trials 1 to 5 (N=55), and (c) a control sample matched on age, education, and race, but not on initial CVLT learning performance (N=55). Current findings indicate that: (a) rate of learning was comparable across groups, consistent with no encoding differences, (b) TBI patients have a significantly more rapid rate of forgetting of new information than either acquisition-matched or demographic-matched controls, consistent with consolidation problems in TBI, (c) TBI patients have less proactive interference than demographic-matched control participants, consistent with a consolidation problem in the TBI group, (d) TBI patients and acquisition-matched controls have comparably low rates of proactive interference, consistent with impaired acquisition in both of these groups, and (e) TBI patients and controls do not differ in the benefit experienced from semantic or recognition retrieval cues, consistent with no differences in retrieval processes. These data support an impaired consolidation hypothesis, rather than encoding or retrieval deficits, as the primary deficit underlying memory impairment in TBI.     

Working Memory and Verbal Fluency Deficits Following Cerebellar Lesions: Relation to Interindividual Differences in Patient Variables

Findings concerning cognitive impairment in patients with focal cerebellar lesions tend to be inconsistent and usually reflect a mild deficit. Patient variables such as lesion age and the age at lesion onset might affect functional reorganization and contribute to the variability of the findings. To assess this issue, 14 patients with focal vascular cerebellar lesions and 14 matched healthy control subjects performed a verbal working memory and a verbal long-term memory task as well as verbal fluency tasks. Patients showed deficits in working memory and verbal fluency, while recall of complex narrative material was intact. Verbal fluency performance correlated significantly with age in the patient group, with more severe impairments in older patients, suggesting that age at lesion onset is a critical variable for cognitive outcome. In controls, no significant correlations with age were observed. Taken together, our findings support the idea of cerebellar involvement in nonmotor functions and indicate the relevance of interindividual differences in regard to clinical parameters after focal cerebellar damage.     

Verbal Memory in Newly Diagnosed Patients and Patients with Chronic Left Temporal Lobe Epilepsy

The objective of this study was to evaluate verbal memory in newly diagnosed and chronic left temporal lobe epilepsy (LTLE). Verbal memory performance of 39 newly diagnosed, previously untreated adult patients with LTLE and 16 patients with chronic LTLE, as well as 46 healthy controls, was analyzed. The patients with newly diagnosed and chronic LTLE had impaired verbal memory performance compared with normal controls. Memory performance was more affected in chronic LTLE. However, preliminary data from 5-year follow-up of 20 newly diagnosed LTLE patients did not show any deterioration in verbal memory performance. The memory impairment was not associated with the etiology of epilepsy or the hippocampal volumes, but was associated with early onset of epilepsy in LTLE and with secondarily generalized seizure type in newly diagnosed LTLE. The results of this study show that verbal memory is impaired not only in chronic LTLE but also in newly diagnosed, untreated LTLE. This suggests that the memory problems observed in patients with chronic LTLE cannot be attributed solely to medication effects or the chronic effects of recurrent seizures.     

Differential Effects of Left and Right Anterior Temporal Lobectomy on Verbal Learning and Memory Performance

The California Verbal Learning Test (CVLT) was utilized to identify the quantitative and qualitative alterations in verbal learning and memory performance that discriminated between patients following partial resection of the left (dominant) (n = 26) or right (nondominant) (n = 31) temporal lobe. Patients were administered the CVLT preoperatively and 6 months postoperatively, and the differential effects of laterality of resection on verbal learning and memory performance were determined. Following left temporal resection, patients showed significantly more serial clustering, a lower proportion of words recalled from the middle of the list, and more intrusion errors in free recall. Patients who underwent right temporal resection showed significantly greater recall of words from the middle and fewer words from the end of the list, more semantic clustering, and greater ability to recall verbal material after a short delay. These findings suggest that anterior temporal lobectomy (ATL) results in changes in the way verbal material is acquired, and affects the rate of forgetting. Patients who undergo left ATL become more dependent on less effective and efficient learning strategies, and forget the material that they have acquired at a faster rate. The opposite tendencies characterize patients who undergo right ATL.     

Functional Plasticity After Left Anterior Temporal Lobectomy: Reconstitution and Compensation of Verbal Memory Functions

Summary: Purpose: This study investigated the functional plasticity of the brain to reconstitute and compensate for verbal memory functions after epilepsy surgery of left temporocortical and temporomesial structures. We hypothesized that memory outcome would be best when surgery is performed within the period of cerebral plasticity, and that the outcome should be worst when fluid intelligence starts to decrease with physiologic aging. We also raised the question of different plasticity and compensation mechanisms for temporomesial and temporocortical memory functions. Methods: We evaluated preoperative and l-year-post- operative memory data and other verbal functions in 104 patients with epilepsy, who underwent a standard left anterior temporal lobe. resection. We used memory measures that had been previously shown to be most selective for mesial and lateral functions, respectively. Determinants of postoperative memory outcome were evaluated by multiple regression analysis. Group statistics were calculated on the basis of the periods that are usually assumed to be significant for plasticity and behavioral compensation. Individual postoperative changes in memory functions were evaluated on the basis of test-retest data obtained in a group of 100 non-surgical patients with localization-related epilepsies (mean retest interval >12 months). Results: Only changes in cortically represented learning and data acquisition were related to age, plasticity, and capacities for behavioral compensation. No patient in the youngest group (younger than 15 years), 33% of patients who had surgery between the ages of 15 and 30 years, and 61% of the patients undergoing surgery older than age 30 years had significant deterioration in verbal learning. In contrast, postoperative changes in temporomesial consolidation/retrieval processes were independent of age at the time of surgery, plasticity, and capacities for behavioral compensation. Conclusions: Our data indicate different time windows for the reconstitution and compensation of mesial and cortical as- pects of memory. Whereas the reconstitution of and compensation for cortical functions appear restricted by decreasing plasticity and physiological aging, mesial functions seem to be reconstituted by contralateral mesial structures over a much longer period. Concerning drug-resistant localization-related epilepsies, our results justify early consideration of surgery, especially when cortical structures are affected.     

Degree of Hippocampal Neuron Loss Determines Severity of Verbal Memory Decrease After Left Anteromesiotemporal Lobectomy

Summary: Fifty-eight left speech dominant adults with medically refractory epilepsy originating from the temporal lobe (28 left, 30 right) were examined using the verbal Selective Reminding Test before and after anteromesiotemporal lobectomy. After neuron density in the excised hippocampal tissue was established, a median split procedure was performed to distinguish patients with severe neuron loss (13 left, 16 right) from those with only mild or moderate neuron loss (15 left, 14 right). The memory of patients with severe left hippocampal neuron loss did not decrease significantly postoperatively. Patients with mild or moderate left hippocampal neuron loss experienced significant verbal memory decrease postoperatively. The magnitude of the verbal memory decrease was not related to recurrence of seizures after operation. Patients undergoing right anteromesiotemporal lobectomy exhibited significant improvements in verbal memory, regardless of the condition of the excised hippocampal tissue. The degree of hippocampal neuron loss determines to a great extent the severity of the verbal memory decrease that follows dominant anteromesiotemporal lobectomy.     

Verbal and Spatial Working Memory in Autism

Verbal and spatial working memory were examined in high-functioning children, adolescents, and adults with autism compared to age and cognitive-matched controls. No deficit was found in verbal working memory in the individuals with autism using an N-back letter task and standardized measures. The distinction between the N-back task and others used previously to infer a working memory deficit in autism is that this task does not involve a complex cognitive demand. Deficits were found in spatial working memory. Understanding the basis for the dissociation between intact verbal working memory and impaired spatial working memory and the breakdown that occurs in verbal working memory as information processing demands are increased will likely provide valuable insights into the neural basis of autism.     

Hippocampal Connectivity with Retrosplenial Cortex is Linked to Neocortical Tau Accumulation and Memory Function

The mechanisms underlying accumulation of Alzheimer''s disease (AD)-related tau pathology outside of the medial temporal lobe (MTL) in older adults are unknown but crucial to understanding cognitive decline. A growing body of evidence from human and animal studies strongly implicates neural connectivity in the propagation of tau in humans, but the pathways of neocortical tau spread and its consequences for cognitive function are not well understood. Using resting state functional magnetic resonance imaging (fMRI) and tau PET imaging from a sample of 97 male and female cognitively normal older adults, we examined MTL structures involved in medial parietal tau accumulation and associations with memory function. Functional connectivity between hippocampus (HC) and retrosplenial cortex (RsC), a key region of the medial parietal lobe, was associated with tau in medial parietal lobe. By contrast, connectivity between entorhinal cortex (EC) and RsC did not correlate with medial parietal lobe tau. Further, greater hippocampal-retrosplenial (HC-RsC) connectivity was associated with a stronger correlation between MTL and medial parietal lobe tau. Finally, an interaction between connectivity strength and medial parietal tau was associated with episodic memory performance, particularly in the visuospatial domain. This pattern of tau accumulation thus appears to reflect pathways of neural connectivity, and propagation of tau from EC to medial parietal lobe via the HC may represent a critical process in the evolution of cognitive dysfunction in aging and AD.SIGNIFICANCE STATEMENT The accumulation of tau pathology in the neocortex is a fundamental process underlying Alzheimer''s disease (AD). Here, we use functional connectivity in cognitively normal older adults to track the accumulation of tau in the medial parietal lobe, a key region for memory processing that is affected early in the progression of AD. We show that the strength of connectivity between the hippocampus (HC) and retrosplenial cortex (RsC) is related to medial parietal tau burden, and that these tau and connectivity measures interact to associate with episodic memory performance. These findings establish the HC as the origin of medial parietal tau and implicate tau pathology in this region as a crucial marker of the beginnings of AD.     

Profiles of Patients with Left Prefrontal and Left Temporal Lobe Lesions after Cerebrovascular Infarcations on California Verbal Learning Test-Like Indices

We compared memory disorders of three patient groups suffering from brain lesions with a word list corresponding to the California Verbal Learning Test (CVLTgcor). Dependent measures were learning rate and efficiency, retention, and strategic control of the learning process. Compared to a control group of patients with right hemispheric lesions, a left Arteria cerebri posterior (LACP) group showed general memory deficits, an inflated recency effect, and increased serial clustering. A left prefrontal cortex (LPFC) group documented slowed learning and increased recall after semantic cues. Discriminant analysis correctly classified 86.11% of the patients. It is argued that (a) the CVLT helps to cover differences in memory disorders recently discussed in cognitive neuropsychology; (b) differences between PFC and ACP patients become evident only if strategic aspects of learning and increased recall after semantic cueing are taken into account. The results are discussed within the framework of recent cognitive neuropsychological findings and with a distinction between fronto-subcortical and cortical memory disorders.     

Concentration and Memory Deficits in Patients with Fibromyalgia Syndrome

The present study compared 30 patients with Fibromyalgia Syndrome (FS) to 30 healthy control subjects matched for age, sex, and estimated intellectual level on standardized measures of attention, concentration, and memory as well as subjective ratings of memory abilities and sleep quality. In addition, in order to investigate the relationship between cognitive functioning and other physical and psychological symptoms, subjects with FS completed psychological measures of pain severity, trait anxiety, and depression. Results indicated that patients with FS performed more poorly on tests of immediate and delayed recall, and sustained auditory concentration, and their ratings of both their memory abilities and sleep quality were lower than those of controls. Furthermore, perceived memory deficits of the FS subjects were disproportionately greater than their objective deficits. Results indicated significant correlations between performance on memory and concentration measures and scores on questionnaires of pain severity and trait anxiety. Implications of these results for multidisciplinary treatment programs are discussed.     

Organizational and Visual Memory Deficits in Schizophrenia and Bipolar Psychoses Using the Rey-Osterrieth Complex Figure: Effects of Duration of Illness

Verbal declarative memory deficits in schizophrenia are well documented whereas visual declarative memory is less studied. Moreover, there are limited data on whether organizational and visual memory deficits are specific to schizophrenic psychoses. We compared visual memory and organizational function in patients with chronic schizophrenia (n = 79) and chronic bipolar psychotic disorder (n = 14), and in healthy controls (n = 84) using the Rey-Osterrieth Complex Figure (ROCF), testing whether organizational impairments (i.e., executive dysfunctions) account for the visual memory deficit. Groups were comparable on age, handedness and expected intellectual ability (based on single word reading). Using analyses of covariance with sex, parental SES and ethnicity as co-variates, patients with schizophrenia were significantly more impaired than controls on copy accuracy, on recall accuracy, and on percent accuracy of recall. Patients with schizophrenia used a more detail-oriented style on copy and recall and had significantly worse recognition memory. After co-varying IQ, copy organization was also significantly different between the groups. Results for accuracy of copy and recall were not significantly attenuated when controlling for copy organization. Duration of illness was associated with visual memory. Bipolar patients performed at an intermediate level between controls and patients with schizophrenia. The data suggest that in schizophrenia, patients have a visual memory disorder characterized by both organizational processing impairments and retention difficulties, and that there is a decline in visual memory functions with duration of illness. Further research is required to determine whether similar mechanisms underlie the neurocognitive deficits in these psychotic disorders.     

Bacterial Alkaloids Mitigate Seizure-Induced Hippocampal Damage and Spatial Memory Deficits

Studies of human patients with temporal lobe epilepsy and animal models of epilepsy have established relationships between seizures, excitotoxic hippocampal damage, and memory impairment. We report that bacterial alkaloids, recently shown to mimic actions of neurotrophic factors in cell culture, attenuate seizure-induced damage to hippocampal neurons and memory impairment in adult rats when administered subcutaneously. Intrahippocampal administration of convulsant doses of kainic acid (KA) to adult rats resulted in degeneration of neurons in CA3, CA1, and hilus. Rats administered KA exhibited (24 h later) deficits in performance on both goal latency and probe trial tasks in Morris water maze (MWM) tests of visuospatial memory. Seizure-induced damage to hippocampal neurons was significantly reduced, to varying extents, in rats administered the bacterial alkaloids K252a, K252b, or staurosporine (daily injections of 4 μg/kg body weight) prior to KA administration. The KA-induced deficits in MWM goal latency performance were abrogated in rats administered K252a or K252b, and K252a and staurosporine completely prevented seizure-induced impairment on the MWM probe trial. The alkaloids did not suppress electroencephalographic seizure activity, suggesting a dissociation between synchronization of activity and synaptically mediated excitotoxic injury to hippocampal neurons. Each alkaloid caused an increase in levels of protein tyrosine phosphorylation as determined by Western blot analysis of hippocampal tissue. Our data indicate that these bacterial alkaloids have potent antiexcitotoxic activities which may have clinical utility in epilepsy and other disorders that involve excitotoxic damage.