Verbal Recognition Memory Research Articles

A genome-wide study of common SNPs and CNVs in cognitive performance in the CANTAB

Psychiatric disorders such as schizophrenia are commonly accompanied by cognitive impairments that are treatment resistant and crucial to functional outcome. There has been great interest in studying cognitive measures as endophenotypes for psychiatric disorders, with the hope that their genetic basis will be clearer. To investigate this, we performed a genome-wide association study involving 11 cognitive phenotypes from the Cambridge Neuropsychological Test Automated Battery. We showed these measures to be heritable by comparing the correlation in 100 monozygotic and 100 dizygotic twin pairs. The full battery was tested in approximately 750 subjects, and for spatial and verbal recognition memory, we investigated a further 500 individuals to search for smaller genetic effects. We were unable to find any genome-wide significant associations with either SNPs or common copy number variants. Nor could we formally replicate any polymorphism that has been previously associated with cognition, although we found a weak signal of lower than expected P-values for variants in a set of 10 candidate genes. We additionally investigated SNPs in genomic loci that have been shown to harbor rare variants that associate with neuropsychiatric disorders, to see if they showed any suggestion of association when considered as a separate set. Only NRXN1 showed evidence of significant association with cognition. These results suggest that common genetic variation does not strongly influence cognition in healthy subjects and that cognitive measures do not represent a more tractable genetic trait than clinical endpoints such as schizophrenia. We discuss a possible role for rare variation in cognitive genomics.

A prospective study of cognitive tests to predict performance on a standardised road test in people with dementia

Previous work by Lincoln and colleagues produced a cognitive test battery for predicting safety to drive in people with dementia. The aim was to check the accuracy of this battery and assess whether it could be improved by shortening it, including additional cognitive tests, and a measure of previous driving. Participants with dementia, who were driving, were recruited. They were assessed on cognitive tests including measures of concentration, executive function, visuospatial perception, verbal recognition memory, and speed of information processing. Patients were then assessed on the Nottingham Neurological Driving Assessment (NNDA) by an approved driving instructor (ADI), blind to cognitive test results. Seventy-five patients were recruited and completed the cognitive tests. Of these, 65 were assessed on the road. These participants were aged 59-88 (mean = 75.2, SD = 6.8) and 49 were men. Time driving varied from 19 to 73 years (mean = 52.5, SD = 10.0). Thirteen participants were unsafe and 52 safe to drive. Using a cut-off of > 0 to indicate safety to drive, the original predictive equations correctly classified 48 (76.2%) of 63 participants with complete data. Logistic regression including additional tests reduced misclassifications. A lower proportion of participants were found to be unsafe on the road than in previous studies. Nevertheless, the previously identified equation predicted safety to drive in most patients. Including additional tests reduced the misclassification rate but requires independent validation. We suggest that the cognitive test battery might be used in clinical practice to identify patients with dementia who would benefit from on-road assessment.

Age-related differences in brain activity during extended continuous word recognition in children

To examine the development of verbal recognition memory in primary-school children, 36 healthy younger children (8–9 years old) and 36 healthy older children (11–12 years old) participated in an ERP study with an extended continuous recognition task. Each word of a series of 30 words was shown randomly for six times interspersed with distracter words. The children were required to make old versus new decisions. The data analyses focused on old/new effects (repetition 1 vs. new word) and multiple repetition effects (repetitions 1 through 5) for the N1, P2, N400, and the late positive complex (LPC, 500–800 ms after stimulus onset). Younger children exhibited a strong P2 multiple repetition effect across left lateral regions, with P2 amplitudes increasing linearly with the number of word repetitions. Compared to younger children, older children exhibited a much stronger N400 old/new effect across parietal regions. Old/new and repetition effects for N1 and LPC were similar in both age groups. Correlational analysis showed that in older children, larger N400 old/new effects on the continuous recognition task were moderately associated with better verbal learning on an auditory verbal learning task. In both age groups, the gain in recognition accuracy over multiple repetitions correlated with the LPC repetition effect. The age differences in P2 repetition effects and N400 old/new effects suggest that in younger children whole-word orthographic representations are dependent on the strength of the memory trace and that lexical–semantic representations develop with age. The LPC results suggest that recollection plays a substantial role in recognition memory of both younger and older children.

Repetition suppression and reactivation in auditory-verbal short-term recognition memory.

The neural response to stimulus repetition is not uniform across brain regions, stimulus modalities, or task contexts. For instance, it has been observed in many functional magnetic resonance imaging (fMRI) studies that sometimes stimulus repetition leads to a relative reduction in neural activity (repetition suppression), whereas in other cases repetition results in a relative increase in activity (repetition enhancement). In the present study, we hypothesized that in the context of a verbal short-term recognition memory task, repetition-related “increases” should be observed in the same posterior temporal regions that have been previously associated with “persistent activity” in working memory rehearsal paradigms. We used fMRI and a continuous recognition memory paradigm with short lags to examine repetition effects in the posterior and anterior regions of the superior temporal cortex. Results showed that, consistent with our hypothesis, the 2 posterior temporal regions consistently associated with working memory maintenance, also show repetition increases during short-term recognition memory. In contrast, a region in the anterior superior temporal lobe showed repetition suppression effects, consistent with previous research work on perceptual adaptation in the auditory–verbal domain. We interpret these results in light of recent theories of the functional specialization along the anterior and posterior axes of the superior temporal lobe.

Reversibility of the effects of acute ovarian hormone suppression on verbal memory and prefrontal function in pre-menopausal women

Whilst acute loss of ovarian function is associated with memory deficits, the biological basis of this is poorly understood. We have previously reported that acute loss of function during Gonadotropin Hormone Releasing Hormone agonists (GnRHa) treatment is associated with impaired verbal memory and a disruption of corresponding left inferior frontal gyrus (LIFG) during the encoding stage. In the current study, we provide a critical extension to this work by determining whether this memory deficit is reversible following normalization of ovarian function. To do this we carried out a further imaging study using the same verbal memory recognition task after cessation of GnRHa-induced ovarian suppression. We used event-related fMRI to study verbal episodic memory performance and brain activation at the LIFG in 13 healthy pre-menopausal women pre-, during, and post-acute ovarian hormone suppression using GnRHa. Following resolution of acute GnRHa-induced ovarian suppression, verbal recognition scores returned to their initial levels and this restoration was associated with a restored level of left frontal activation during successful encoding of words. Our findings suggest that the memory deficits associated with acute ovarian suppression are reversed following resolution of normal ovarian function and are associated with reversible attenuation of LIFG activation during encoding. These findings lend further support to the hypothesis that memory difficulties reported by some women following acute ovarian hormone withdrawal are reversible and may have a clear neurobiological basis.

Impairment of short‐term memory associated with low iron stores in a volunteer multidose plateletpheresis donor

A platelet donor may lose 80-100 mL of blood both in the harness and by blood sampling at each donation, the equivalent of four to five whole blood donations per annum for a donor attending at 2-weekly intervals. A 54-year-old male multidose platelet donor had donated platelets at regular 2-weekly intervals for 6 years. He developed an impairment of anterograde memory (new learning). A self-rating scale revealed a moderate degree of depression [Beck Depression Inventory (BDI) score 22]. Memory testing (Doors and People Memory Battery) showed low scores, particularly for verbal recall and verbal recognition memory. He was found to have a normal haemoglobin of 157 g L(-1) with normal red blood cell indices, but a low serum ferritin (15 ng mL(-1)) and a low serum iron (8.1 mmol L(-1)). Following iron therapy and a return of his iron stores to normal levels, there was an improved BDI score of 13 (minimal level of depression) and a marked improvement in memory test scores. This has been maintained even though he has resumed platelet donation but at reduced intervals.

Impairment of verbal recollection following ischemic damage to the right anterior hippocampus

Damage to the left medial temporal lobe (MTL) leads to an impairment of verbal recognition memory, affecting both the process of conscious recollection and familiarity-based recognition. Neuroimaging evidence, on the other hand, suggests a bilateral MTL contribution to verbal recollection. We investigated verbal recognition memory in three patients with focal ischemic lesions to the right MTL. The dual-process signal detection model and the process-dissociation procedure were applied to assess the contributions of recollection and familiarity to recognition memory. Compared to a group of 27 healthy age-matched controls, patients were impaired at recollection while familiarity was intact, and this effect was found for both estimation procedures. Detailed single-case analyses confirmed this pattern in two of the three right MTL patients. The findings suggest that, when task demands are high, as during recollective recognition, the right anterior hippocampus may also contribute to verbal recollection, thereby confirming neuroimaging evidence of a joint involvement of the left and the right MTL in verbal recollection.

Compensatory brain activation for recognition memory in patients with medication-resistant epilepsy

Progressive decline of memory functions has been observed in patients with chronic medication-resistant epilepsy. The progression likely relates to the effects of epileptiform discharges, seizures, and medications on the processes of encoding and retrieval. The goal of the study described here was to use functional MRI (fMRI) to examine the effects of chronic epilepsy on verbal recognition memory. We enrolled 12 patients with medication-resistant epilepsy (5 with right and 7 with left hemispheric seizure onset) and 18 healthy controls matched for age, gender, and handedness. Subjects underwent fMRI at 3T using a word recognition task during which they had to recall if words presented during scanning were words they had learned prior to scanning. Although we noted many similarities in the fMRI activation patterns between the subjects with epilepsy and the healthy subjects in areas typically involved in memory processing, testing of the interaction effects for target-foil differences between groups revealed several differences in activation including the right insula, the left cuneus, and the bilateral subgenual anterior cingulate cortex (ACC). In patients with epilepsy, these regions exhibited greater activation for targets than foils, but in healthy subjects the difference was reversed (right insula), absent (left cuneus), or included deactivation to target words (pregenual ACC). These differences were seen despite similar performance during the memory task, suggesting that activations observed in these additional regions may represent compensatory processes for verbal recognition memory that are induced by chronic brain injury related to recurrent seizures.

Quality of Life and Memory after Vagus Nerve Stimulator Implantation for Epilepsy

This prospective, case control study evaluates quality of life (QOL), depressive affect, and memory outcomes of epilepsy patients implanted with a vagus nerve stimulator (VNS). Three groups of patients with epilepsy underwent assessment on two occasions: 1) patients with a VNS were tested before and 12 months after implantation (n = 16); 2) patients who underwent cerebral resective surgery were tested pre- and post-operatively (n = 10); and 3) patients under medical management (n = 9). Group means were compared on the QOLIE-89, Geriatric Depression Scale, Wechsler Memory Scale - III, and the Memory Observation Questionnaire. Secondary analyses calculated the reliable change index, providing information on change beyond measurement error and chance. Mean ratings of QOL, depression, and memory complaints and objective memory scores remained stable or improved in all the groups. The QOL improved more after cerebral resective surgery than VNS or medication controls, but the VNS and medication control groups did not differ. In the VNS group, QOL was not related to seizure reduction. The percentage of cases showing real change in memory was equivalent across groups, except in one of eight indices (i.e., verbal recognition memory). This first case controlled design found that vagus nerve stimulation as an adjunctive therapy for seizure control did not change QOL, depressive affect, or objective memory scores over one-year more so than medical management alone. We point out the need for larger case control, non-industry funded investigations.

Five-year follow-up of unilateral posteroventral pallidotomy in Parkinson's disease

Background Neurocognitive outcome research of individuals with Parkinson's disease after unilateral pallidotomy is inconsistent. Although some studies reported few cognitive changes, other investigations have more consistently shown both transient and long-term cognitive decline postoperatively. Methods We report the long-term motor and neurocognitive outcome 5 years post surgery for 18 patients with Parkinson's disease (12 men and 6 woman; all right-handed) who underwent right or left unilateral posteroventral pallidotomy. Results Pallidotomy patients revealed long-term motor benefits from the surgery in their “off” state and control of dopa-induced dyskinesias in their “on” state, which is consistent with previous research. We found mild declines in oral and visuomotor information processing speed, verbal recognition memory, and mental status 5 years after surgery, which differs from previous literature regarding the long-term neurocognitive outcome after pallidotomy. Differences between the right and left pallidotomy patients for both motor and cognitive skills were not found. Conclusion Although deep brain stimulation is presently the treatment of choice, pallidotomy continues to be performed around the world. Consequently, although unilateral pallidotomy should be considered a treatment option for patients with Parkinson's disease who suffer from severe unilateral disabling motor symptoms or dyskinesias, the long-term neurocognitive outcome should also be considered in treatment decisions.

Neuropsychological task performance in bipolar spectrum illness: genetics, alcohol abuse, medication and childhood trauma

Impaired executive and memory function is a putative genetic trait marker of bipolar I disorder (BPD I). Although executive/memory function has been posited to be an endophenotype of BPD I, it is unclear whether this extends to bipolar spectrum illness. It is also unclear to what extent non-genetic factors such as childhood abuse, alcoholism and medication influence neurocognitive function. We assessed the neuropsychological performance of a large cohort of bipolar disorder probands and their affectively ill and healthy family members, while controlling for self-reported childhood sexual and emotional abuse, emotional neglect, alcohol abuse and medication. A total of 230 largely euthymic participants from 47 families, comprising 49 subjects with BPD I, 19 with bipolar II disorder (BPD II), 44 with recurrent major depression (MDE-R), 33 with a single lifetime episode of depression (MDE-S), 20 with other DSM-IV diagnoses and 65 unaffected relatives, were assessed with a battery of neuropsychological tasks. Sexual abuse, emotional abuse and emotional neglect scores were associated with poorer cognitive performance. After controlling for childhood trauma, the BPD I group performed worse than unaffected relatives on tests of visual recall memory as well as verbal recall and recognition memory. In contrast, individuals with BPD II and bipolar spectrum illness did not differ significantly from unaffected relatives. Treatment with lithium and antipsychotic medication was associated with reduced executive and verbal recognition memory function. After controlling for medication and other covariates, only verbal recall memory was significantly impaired in the BPD I cohort. Verbal recall deficits may be one manifestation of a genetically driven dysfunction of frontal-striatal cortical networks in BPD I.

The use of self-generation procedures facilitates verbal memory in individuals with seizure disorders

The efficacy of a self-generation encoding procedure in facilitating the encoding and retrieval of verbal memories was compared with the didactic presentation of information in individuals with seizure disorders. Through a within-subject design, 87 patients (25 left temporal seizure onset, 29 right temporal, 8 frontal, and 25 psychogenic nonepileptic seizures) received a self-generation learning condition and a didactic learning condition and were subsequently tested for verbal paired associate free recall, cued recall, and recognition memory. All patient groups benefited from the use of the self-generation condition relative to the didactic condition. Better performance occurred with the self-generation procedure for cued recall and recognition memory test performance, but not free recall. Individuals with a left temporal seizure onset (patients with the poorest memory performance on the didactic condition) benefited the most from the self-generation condition. A memory encoding strategy that actively involves patient participation enhances memory performance.

Cocaine Users Differ from Normals on Cognitive Tasks Which Show Poorer Performance During Drug Abstinence

Seventeen non-treatment seeking cocaine-dependent individuals participated in three-week longitudinal inpatient studies of cognitive changes during drug use and abstinence. Protocols included three days drug-free baseline, three days cocaine self-administration, and two weeks complete abstinence. A repeatable cognitive battery showed attention and delayed verbal recognition memory but not working memory to be impaired in cocaine users compared to age- and sex-matched normative values. Attention was significantly poorer during the first and second week of abstinence compared to days on which cocaine was used suggesting that certain cocaine-induced impairments may be acutely normalized by cocaine use, but resurface during abstinence.

Acute nicotine improves cognitive deficits in young adults with attention-deficit/hyperactivity disorder

Objective The strong association between ADHD and cigarette smoking and the known effects of nicotine on cognition has lead to interest in the role of cholinergic function in ADHD cognitive deficits. We have previously demonstrated that acute nicotine improves behavioral inhibition in adolescents with ADHD. This study examined acute nicotine in young adults with ADHD-Combined type on cognitive domains including behavioral inhibition, delay aversion, and recognition memory. Methods 15 non-smoking young adults (20 ± 1.7 years) diagnosed with ADHD-C received acute nicotine (7 mg patch for 45 min) and placebo on separate days. Cognitive tasks included the Stop Signal Task, Choice Delay task, and the High–Low Imagery Task (a verbal recognition memory task). Three subjects experienced side effects and their data was excluded from analysis of cognitive measures. Results There was a significant ( p < .05) positive effect of nicotine on the Stop Signal Reaction Time measure of the Stop Signal Task. The SSRT was improved without changes in GO reaction time or accuracy. There was a trend ( p = .09) for nicotine to increase tolerance for delay and a strong trend ( p = .06) for nicotine to improve recognition memory. Conclusions Non-smoking young adults with ADHD-C showed improvements in cognitive performance following nicotine administration in several domains that are central to ADHD. The results from this study support the hypothesis that cholinergic system activity may be important in the cognitive deficits of ADHD and may be a useful therapeutic target.

BDNF Val 66Met polymorphism significantly affects d′ in verbal recognition memory at short and long delays

A functional polymorphism at the val66met locus in the BDNF gene has significant effects on the pro-form of the protein in intracellular trafficking and activity-dependent, but not constitutive, secretion. These differences are thought to underlie several findings in humans related to this polymorphism, including markers of neuronal viability, BOLD activation in medial temporal lob regions, and some aspects of behavior. However, many important questions remain about the impact of BDNF on various mnemonic subprocesses at the behavioral level. In this study, we examined the impact of the val/met polymorphism in a verbal recognition memory paradigm involving manipulation of depth of encoding and differential delays for recall and analyses of hits for previously presented target words and correct rejections of foils. Twenty-four human val homozygous individuals and 24 met carrier individuals comprised the sample. All were healthy controls. IQ between the groups was equivalent. In the encoding phase of the study, words were presented and encoded either by a decision as to whether they were living or nonliving (“deep”) or if they contained the letter “A” (shallow). After this phase, recognition was tested immediately, half an hour, and 24 h later. BDNF genotype had significant effects on hits and discriminability ( d′), accounting for at least 10% of the variance, but not on correct rejections or beta. BDNF did not interact with level of encoding, nor did it interact with delay. In sum, BDNF genotypes impacted “hits” in a recognition memory paradigm, findings consistent with the general notion that BDNF plays a prominent role in memory subprocesses thought to engage the medial temporal lobe.

Recent Neuroimaging Techniques in Mild Traumatic Brain Injury

Recent Neuroimaging Techniques in Mild Traumatic Brain Injury

Genotype and Childhood Sexual Trauma Moderate Neurocognitive Performance: A Possible Role for Brain-Derived Neurotrophic Factor and Apolipoprotein E Variants

Limited success in the identification of genetic variants underpinning psychiatric illness has prompted attempts to elucidate gene-environment interactions and illness-associated endophenotypes. Here we measured childhood sexual abuse, a potential environmental risk factor, and verbal and visual recall and recognition memory, a possible illness-associated endophenotype in a cohort of bipolar disorder (BPD) subjects and their relatives. We predicted that memory would be affected by sexual trauma and that a number of functional polymorphisms previously implicated in BPD and cognition would moderate the effect of psychological trauma on memory. A cohort of 350 individuals from 47 BPD families was recruited, tested with a neuropsychological battery, and given the Childhood Trauma Questionnaire (CTQ). Eleven different genetic variants previously found to be relevant to BPD or memory dysfunction were typed. As predicted, scores on the sexual abuse scale of the CTQ were negatively associated with memory performance. Furthermore, the low-activity Met allele of the brain-derived neurotrophic factor (BDNF) gene and the epsilon4 allele of the apolipoprotein E gene interacted with sexual abuse scores to result in reduced memory test performance. Apolipoprotein E and BDNF exert a neurotrophic effect in response to cellular injury. Their possible moderation of the association between sexual abuse and memory performance might indicate that there is some degree of overlap in the pathophysiological mechanisms by which psychological and physical trauma impact brain function. The finding of an environmental effect on memory performance and a gene-environment interaction on this hypothetical endophenotype of BPD illustrates the difficulty of identifying genetically and phenotypically simple intermediate traits for molecular genetic studies.

I. Longitudinal changes in aging brain function

Changes in brain activity over time were evaluated in a group of older adults in the Baltimore Longitudinal Study of Aging who maintained good physical and cognitive health. Participants underwent PET scans during rest and delayed verbal and figural recognition memory performance at year 1 baseline and at year 9. While memory performance remained stable over the 8 years, longitudinal changes in regional cerebral blood flow were observed within each scan condition. Further analyses revealed distinctive patterns of change related specifically to verbal or figural recognition, as well as longitudinal changes common to all scan conditions. These findings demonstrate that the older brain undergoes functional reorganization with increasing age in healthy, cognitively stable individuals. In view of the stable memory performance, the task-dependent results suggest that age-related changes in brain activity help maintain cognitive function with advancing age.

II. Temporal patterns of longitudinal change in aging brain function

Time-dependent changes in brain activity were assessed in a group of older adults who maintained good physical and cognitive health at years 1, 3, 5, 7, and 9 of the Baltimore Longitudinal Study of Aging neuroimaging study. Each year, these participants underwent PET scans during rest and delayed verbal and figural recognition memory conditions. While memory performance remained stable over the 8 years, both generalized and modality-specific patterns of time-dependent changes in regional cerebral blood flow (rCBF) were found. Many brain regions showed steady, progressive changes in rCBF over the 8 years while others maintained rCBF for a number of years before showing incremental declines or increases in activity. These temporal patterns of change were observed in many regions of the brain, particularly in the frontal and temporal lobes, suggesting that there are distinctive patterns of age-related functional decline and compensatory activity over time. The precise patterns of regional involvement and the temporal dynamics of rCBF change within specific regions vary based on cognitive processing demands.

Fractionation of memory in medial temporal lobe amnesia

We report a comprehensive investigation of the anterograde memory functions of two patients with memory impairments (RH and JC). RH had neuroradiological evidence of apparently selective right-sided hippocampal damage and an intact cognitive profile apart from selective memory impairments. JC, had neuroradiological evidence of bilateral hippocampal damage following anoxia due to cardiac arrest. He had anomic and “executive” difficulties in addition to a global amnesia, suggesting atrophy extending beyond hippocampal regions. Their performance is compared with that of a previously reported hippocampal amnesic patient who showed preserved recollection and familiarity for faces in the context of severe verbal and topographical memory impairment [VC; Cipolotti, L., Bird, C., Good, T., Macmanus, D., Rudge, P., & Shallice, T. (2006). Recollection and familiarity in dense hippocampal amnesia: A case study. Neuropsychologia, 44, 489–506.] The patients were administered experimental tests using verbal (words) and two types of non-verbal materials (faces and buildings). Receiver operating characteristic analyses were used to estimate the contribution of recollection and familiarity to recognition performance on the experimental tests. RH had preserved verbal recognition memory. Interestingly, her face recognition memory was also spared, whilst topographical recognition memory was impaired. JC was impaired for all types of verbal and non-verbal materials. In both patients, deficits in recollection were invariably associated with deficits in familiarity. JC's data demonstrate the need for a comprehensive cognitive investigation in patients with apparently selective hippocampal damage following anoxia. The data from RH suggest that the right hippocampus is necessary for recollection and familiarity for topographical materials, whilst the left hippocampus is sufficient to underpin these processes for at least some types of verbal materials. Face recognition memory may be adequately subserved by areas outside of the hippocampus.