Declarative Memory Function Research Articles

Abstract TMP97: Demyelination, Cognition and Imaging in a Translational Model of Rat Vascular Cognitive Impairment

Small vessel disease and/or atherosclerosis produce microvascular and parenchymal inflammation in white matter and results in vascular cognitive impairment (VCI). We have performed bilateral carotid artery stenosis in hypertensive rats (SHR) to better understand disease pathology, targets for intervention and markers. Hypothesis: Complex cognitive deficits and diffuse fiber tract changes relevant to human VCI can be quantified and validated for future use. Methodology: We performed a series of behavioral assays to test declarative memory and executive functioning in stenosis compared to sham surgery SHR. Behavioral assays included T-maze decision making and alternation, novel object recognition (NOR) and active place avoidance (APA). MRI (DTI, DWI, Arterial Spin Labeling; ASL) and FDG-PET imaging was done in Corpus Callosum (CC). Histology-immunohistochemistry included measurements of microglia (Iba-1), astrocytes (GFAP) and Luxol fast blue (for myelin) in CC. Results: Stenosis resulted in consistent executive function decision making (T-maze) deficits (p<0.05) and impaired complex cognitive performance (APA). No significant differences occurred between sham and stenosis animals in NOR and T-maze alternation. DTI analysis indicated significant (p<0.05) changes in the CC of stenosis compared to sham SHR including: (1) decreased fractional anisotropy, (2) increased radial diffusivity, and (3) unchanged axial diffusivity. MRI ASL revealed significant (p<0.05) decreases in white matter perfusion. No significant changes were seen in FDG-PET. In summary, stenosis animals exhibited increased white matter glial cell inflammation related to demyelination and lost cognition. The inflammatory microglia phenotype was verified using TNFα plus Iba-1 double staining. CC changes were significantly (p<0.05) greater in the anterior, periventricular forebrain. Conclusion: We have successfully modeled the behavioral, imaging and histologic profile of human VCI in the rat. Currently pre/mature oligodendrocyte changes are being evaluated. This approach provides future opportunities to localize forebrain white matter changes using MR imaging parameters as markers for monitoring VCI demyelination/pathology and intervention.

Motor skill learning and offline-changes in TGA patients with acute hippocampal CA1 lesions

Learning and the formation of memory are reflected in various memory systems in the human brain such as the hippocampus based declarative memory system and the striatum-cortex based system involved in motor sequence learning. It is a matter of debate how both memory systems interact in humans during learning and consolidation and how this interaction is influenced by sleep. We studied the effect of an acute dysfunction of hippocampal CA1 neurons on the acquisition (on-line condition) and off-line changes of a motor skill in patients with a transient global amnesia (TGA). Sixteen patients (68 ± 4.4 yrs) were studied in the acute phase and during follow-up using a declarative and procedural test, and were compared to controls. Acute TGA patients displayed profound deficits in all declarative memory functions. During the acute amnestic phase, patients were able to acquire the motor skill task reflected by increasing finger tapping speed across the on-line condition, albeit to a lesser degree than during follow-up or compared to controls. Retrieval two days later indicated a greater off-line gain in motor speed in patients than controls. Moreover, this gain in motor skill performance was negatively correlated to the declarative learning deficit. Our results suggest a differential interaction between procedural and declarative memory systems during acquisition and consolidation of motor sequences in older humans. During acquisition, hippocampal dysfunction attenuates fast learning and thus unmasks the slow and rigid learning curve of striatum-based procedural learning. The stronger gains in the post-consolidation condition in motor skill in CA1 lesioned patients indicate a facilitated consolidation process probably occurring during sleep, and suggest a competitive interaction between the memory systems. These findings might be a reflection of network reorganization and plasticity in older humans and in the presence of CA1 hippocampal pathology.

Human Hippocampal Dynamics during Response Conflict

Besides its relevance for declarative memory functions, hippocampal activation has been observed during disambiguation of uncertainty and conflict. Uncertainty and conflict may arise on various levels. On the perceptual level, the hippocampus has been associated with signaling of contextual deviance and disambiguation of similar items (i.e., pattern separation). Furthermore, conflicts can occur on the response level. Animal experiments showed a role of the hippocampus for inhibition of prevailing response tendencies and suppression of automatic stimulus-response mappings, potentially related to increased theta oscillations (3-8 Hz). In humans, a recent fMRI study demonstrated hippocampal involvement in approach-avoidance conflicts. However, the more general significance of hippocampal activity for dealing with response conflicts also on a cognitive level is still unknown. Here, we investigated the role of the hippocampus for response conflict in the Stroop task by combining intracranial electroencephalography (iEEG) recordings from the hippocampus of epilepsy patients with region of interest-based fMRI in healthy participants. Both methods revealed converging evidence that the hippocampus is recruited in a regionally specific manner during response conflict. Moreover, our iEEG data show that this activation depends on theta oscillations and is relevant for successful response conflict resolution.

Focalised stimulation using high definition transcranial direct current stimulation (HD-tDCS) to investigate declarative verbal learning and memory functioning

BackgroundDeclarative verbal learning and memory are known to be lateralised to the dominant hemisphere and to be subserved by a network of structures, including those located in frontal and temporal regions. These structures support critical components of verbal memory, including working memory, encoding, and retrieval. Their relative functional importance in facilitating declarative verbal learning and memory, however, remains unclear. ObjectiveTo investigate the different functional roles of these structures in subserving declarative verbal learning and memory performance by applying a more focal form of transcranial direct current stimulation, “High Definition tDCS” (HD-tDCS). Additionally, we sought to examine HD-tDCS effects and electrical field intensity distributions using computer modelling. MethodsHD-tDCS was administered to the left dorsolateral prefrontal cortex (LDLPFC), planum temporale (PT), and left medial temporal lobe (LMTL) to stimulate the hippocampus, during learning on a declarative verbal memory task. Sixteen healthy participants completed a single blind, intra-individual cross-over, sham-controlled study which used a Latin Square experimental design. Cognitive effects on working memory and sustained attention were additionally examined. ResultsHD-tDCS to the LDLPFC significantly improved the rate of verbal learning (p=0.03, η2=0.29) and speed of responding during working memory performance (p=0.02, η2=0.35), but not accuracy (p=0.12, η2=0.16). No effect of tDCS on verbal learning, retention, or retrieval was found for stimulation targeted to the LMTL or the PT. Secondary analyses revealed that LMTL stimulation resulted in increased recency (p=0.02, η2=0.31) and reduced mid-list learning effects (p=0.01, η2=0.39), suggesting an inhibitory effect on learning. ConclusionsHD-tDCS to the LDLPFC facilitates the rate of verbal learning and improved efficiency of working memory may underlie performance effects. This focal method of administrating tDCS has potential for probing and enhancing cognitive functioning.

Synaptic proteins in the hippocampus indicative of increased neuronal activity in CA3 in schizophrenia.

In schizophrenia, hippocampal perfusion is increased and declarative memory function is degraded. Based on an a priori model of hippocampal dysfunction in schizophrenic psychosis, the authors postulated molecular and cellular changes in CA3 consistent with increased NMDA receptor signaling. Postmortem hippocampal subfield tissue (CA3, CA1) from subjects with schizophrenia and nonpsychiatric comparison subjects was analyzed using Western blotting and Golgi histochemistry to examine the hypothesized outcomes. The GluN2B-containing NMDA receptors (GluN2B/GluN1) and their associated postsynaptic membrane protein PSD95 were both increased in schizophrenia in CA3 tissue, but not in CA1 tissue. Quantitative analyses of Golgi-stained hippocampal neurons showed an increase in spine density on CA3 pyramidal cell apical dendrites (stratum radiatum) and an increase in the number of thorny excrescences. The hippocampal data are consistent with increased excitatory signaling in CA3 and/or with an elevation in silent synapses in CA3, a state that may contribute to an increase in long-term potentiation in CA3 with subsequent stimulation and "unsilencing." These changes are plausibly associated with increased associational activity in CA3, with degraded declarative memory function, and with formation of false memories with psychotic content. The influence of these hyperactive hippocampal projections on targets in the limbic neocortex could contribute to components of schizophrenia manifestations in other cerebral regions.

Cognitive deficits in unipolar major depression

Cognitive deficits are common symptom presentations in neurology and psychiatry. Cognitive symptoms during major depressive episodes cause subjective distress as well as difficulties during therapy and psychosocial reintegration. Depression-associated cognitive symptoms are characterized by a mood-congruent information processing bias as well as by cognitive performance deficits. A diagnostically relevant profile of neuropsychological impairments specific to depression has not yet been identified. Nevertheless, deficits of executive and declarative memory functions have repeatedly been reported. The time course of cognitive deficits after remission of mood is not entirely clear. Depending on the point of time of the reinvestigation, patients may still exhibit pronounced cognitive deficits. This article presents the current knowledge about cognitive symptoms in major depression, including the pathophysiology and treatment options.

Temporal lobe surgery in childhood and neuroanatomical predictors of long-term declarative memory outcome.

The temporal lobes play a prominent role in declarative memory function, including episodic memory (memory for events) and semantic memory (memory for facts and concepts). Surgical resection for medication-resistant and well-localized temporal lobe epilepsy has good prognosis for seizure freedom, but is linked to memory difficulties in adults, especially when the removal is on the left side. Children may benefit most from surgery, because brain plasticity may facilitate post-surgical reorganization, and seizure cessation may promote cognitive development. However, the long-term impact of this intervention in children is not known. We examined memory function in 53 children (25 males, 28 females) who were evaluated for epilepsy surgery: 42 underwent unilateral temporal lobe resections (25 left, 17 right, mean age at surgery 13.8 years), 11 were treated only pharmacologically. Average follow-up was 9 years (range 5-15). Post-surgical change in visual and verbal episodic memory, and semantic memory at follow-up were examined. Pre- and post-surgical T1-weighted MRI brain scans were analysed to extract hippocampal and resection volumes, and evaluate post-surgical temporal lobe integrity. Language lateralization indices were derived from functional magnetic resonance imaging. There were no significant pre- to postoperative decrements in memory associated with surgery. In contrast, gains in verbal episodic memory were seen after right temporal lobe surgery, and visual episodic memory improved after left temporal lobe surgery, indicating a functional release in the unoperated temporal lobe after seizure reduction or cessation. Pre- to post-surgical change in memory function was not associated with any indices of brain structure derived from MRI. However, better verbal memory at follow-up was linked to greater post-surgical residual hippocampal volumes, most robustly in left surgical participants. Better semantic memory at follow-up was associated with smaller resection volumes and greater temporal pole integrity after left temporal surgery. Results were independent of post-surgical intellectual function and language lateralization. Our findings indicate post-surgical, hemisphere-dependent material-specific improvement in memory functions in the intact temporal lobe. However, outcome was linked to the anatomical integrity of the temporal lobe memory system, indicating that compensatory mechanisms are constrained by the amount of tissue which remains in the operated temporal lobe. Careful tailoring of resections for children undergoing epilepsy surgery may enhance long-term memory outcome.

Loss of pattern separation performance in schizophrenia suggests dentate gyrus dysfunction

Motivated by evidence that the dentate gyrus differentially mediates the pattern separation (PS) component of declarative memory function and that dentate gyrus harbors molecular and cellular pathologies in schizophrenia, we examined whether PS performance is altered in volunteers with schizophrenia (SZV) relative to healthy volunteers (HV). In groups of well-characterized SZV (n=14) and HV (n=15), we contrasted performance on the Behavioral Pattern Separation (BPS) Task, acquiring two outcome measures, a PS parameter and a Recognition Memory (RM) parameter, as well as specific recognition data by stimulus type. The SZVs showed a significant decrement in PS performance relative to HV (mean±SEM, SZV: 3.1±2.7%; HV: 17.1±5.8%; p=0.039, d′=0.86); whereas SZV and HV did not significantly differ in RM performance (SZV: 50.1±8.1%; HV: 59.3±5.5%; p=0.350, d′=0.36). Moreover, the SZVs showed a selective defect in correctly identifying similar lure items (SZV: 24.0±3.7%; HV: 41.2±4.6%; p<0.05), but demonstrated no impairment in identifying targets and novel foils. These data suggest that the dentate gyrus is dysfunctional in schizophrenia, a feature that could contribute to declarative memory impairment in the disorder and possibly to psychosis, a conclusion consistent with the considerable molecular pathology in the dentate gyrus in schizophrenia.

Memory outcome one year after stereotactic interstitial radiosurgery in patients with epilepsy due to hypothalamic hamartomas

Epileptic seizures caused by hypothalamic hamartomas (HHs) are highly pharmacoresistant. Resective surgical approaches have shown some efficacy in controlling seizures; however, they bear a significant risk of postoperative mnemonic deterioration due to the close anatomical proximity of the HHs to structures essential for memory functions.We report on cognitive outcome in 26 patients with structural epilepsy due to HHs one year after interstitial radiosurgery. Individually, deteriorations occurred more frequently in declarative memory functions (in 20 to 50% of the patients), whereas more than 80% of the patients revealed stable or even improved performance in attentional functions. Preoperative better memory functions were associated with higher risk of postoperative performance decline. After radiosurgery, half of the patients showed more than 50%, and some up to 90%, of seizure reduction. Hypothalamic hamartoma volumes were significantly reduced at follow-up. Transient radiogenic edema found in 10/26 patients was not associated with further cognitive decline after radiosurgery.These results are highly relevant for therapeutic decisions and patient consultation on timing and choice of nonmedical treatment options for HHs.

Investigation of the Component Processes Involved in Verbal Declarative Memory Function in Bipolar Disorder: Utility of the Hopkins Verbal Learning Test-Revised

Evidence suggests that standard learning and recall indexes are sensitive markers of verbal declarative memory ability in bipolar disorder (BD), but no study has examined performance across the full range of component process measures on the Hopkins Verbal Learning Test (HVLT-R) in a BD cohort. As the HVLT-R is part of a widely used battery of cognitive functioning backed by the U.S. Federal Drug Administration as the accepted battery for use in pro-cognitive trials assessing cognitive-enhancing drugs in the related disorder schizophrenia, estimating the utility of its measures in BD is important. Forty-nine BD patients and 51 healthy controls completed the HVLT-R, which was scored for 13 variables of interest, across 4 indices: recall and learning, recognition, strategic organization, and errors. BD patients had greater difficulty in learning the HVLT-R word list compared to controls. They also demonstrated impairment in delayed recall/recognition. There were no differences between the groups in terms of their slope of learning, retrieval index, retention percentage, semantic or serial clustering, errors, or level of retrieval. This pattern was consistent across symptomatic and euthymic patients. The HVLT-R has some utility in characterizing the component processes involved in memory function in BD, such that memory impairments appear to be attributable to deficient encoding processes during the acquisition phase of learning. In the case of planning pro-cognitive clinical trials, the encoding deficits in BD observed here may be sensitive enough to potentially respond to medications designed to enhance the verbal memory performance.

Cognitive Impairment in Cocaine Users is Drug-Induced but Partially Reversible: Evidence from a Longitudinal Study

Cocaine users consistently display cognitive impairments. However, it is still unknown whether these impairments are cocaine-induced and if they are reversible. Therefore, we examined the relation between changing intensity of cocaine use and the development of cognitive functioning within 1 year. The present data were collected as part of the longitudinal Zurich Cocaine Cognition Study (ZuCo(2)St). Forty-eight psychostimulant-naive controls and 57 cocaine users (19 with increased, 19 with decreased, and 19 with unchanged cocaine use) were eligible for analysis. At baseline and after a 1-year follow-up, cognitive performance was measured by a global cognitive index and four neuropsychological domains (attention, working memory, declarative memory, and executive functions), calculated from 13 parameters of a broad neuropsychological test battery. Intensity of cocaine use was objectively determined by quantitative 6-month hair toxicology at both test sessions. Substantially increased cocaine use within 1 year (mean +297%) was associated with reduced cognitive performance primarily in working memory. By contrast, decreased cocaine use (-72%) was linked to small cognitive improvements in all four domains. Importantly, users who ceased taking cocaine seemed to recover completely, attaining a cognitive performance level similar to that of the control group. However, recovery of working memory was correlated with age of onset of cocaine use-early-onset users showed hampered recovery. These longitudinal data suggest that cognitive impairment might be partially cocaine-induced but also reversible within 1 year, at least after moderate exposure. The reversibility indicates that neuroplastic adaptations underlie cognitive changes in cocaine users, which are potentially modifiable in psychotherapeutical or pharmacological interventions.

Pain anticipation recruits the mesolimbic system and differentially modulates subsequent recognition memory

The ability to encode information into long-term memory is not a passive process but can be influenced by motivational factors. While the mesolimbic system has long been associated with reward-driven memory enhancement, the precise neurobiology of processing aversive events and their effects on declarative learning remain unclear. To address this issue, human subjects encoded a series of scene images, which was combined with cues predicting an aversive electric shock with different probabilities (0.2, 0.5, 0.8). Subsequently, recognition memory for the scenes was tested using a remember/know procedure. In a behavioral experiment, shock probability had linear effects on familiarity and inverted u-shaped effects on recollection. While the behavioral effect was absent in experiment 2 (fMRI), at the neural level encoding-related activity in the hippocampus mimicked the recollection specific quadratic effect, whereas activity in the anterior parahippocampal gyrus mirrored the familiarity specific linear relationship that was evident in experiment 1. Importantly, the probability of upcoming shocks was linearly coded in the substantia nigra / ventral tegmental area, and pain associated brain regions, such as the insula, responded to shock delivery. Our results demonstrate that anticipating primary aversive events recruits the human mesolimbic system and differentially modulates declarative memory functions via medial temporal lobe structures.

Functional connectivity changes differ in early and late-onset alzheimer's disease

At a similar stage, patients with early onset Alzheimer's disease (EOAD) have greater neocortical but less medial temporal lobe dysfunction and atrophy than the late-onset form of the disease (LOAD). Whether the organization of neural networks also differs has never been investigated. This study aims at characterizing basal functional connectivity (FC) patterns of EOAD and LOAD in two groups of 14 patients matched for disease duration and severity, relative to age-matched controls. All subjects underwent an extensive neuropsychological assessment. Magnetic resonance imaging was used to quantify atrophy and resting-state FC focusing on : the default mode network (DMN), found impaired in earlier studies on AD, and the anterior temporal network (ATN) and dorso-lateral prefrontal network (DLPFN), respectively involved in declarative memory and executive functions. Patterns of atrophy and cognitive impairment in EOAD and LOAD were in accordance with previous reports. FC within the DMN was similarly decreased in both EOAD and LOAD relative to controls. However, a double-dissociated pattern of FC changes in ATN and DLPFN was found. EOAD exhibited decreased FC in the DLPFN and increased FC in the ATN relative to controls, while the reverse pattern was found in LOAD. In addition, ATN and DLPFN connectivity correlated respectively with memory and executive performances, suggesting that increased FC is here likely to reflect compensatory mechanisms. Thus, large-scale neural network changes in EOAD and LOAD endorse both common features and differences, probably related to a distinct distribution of pathological changes.

Word List and Story Recall Elicit Different Patterns of Memory Deficit in Patients with Alzheimer's Disease, Frontotemporal Dementia, Subcortical Ischemic Vascular Disease, and Lewy Body Dementia

Different roles have been attributed to mesio-temporal areas and frontal lobes in declarative memory functioning, and qualitative differences have been observed in the amnesic symptoms due to pathological damage of these two portions of the central nervous system. The aim of the present study was to look for memory profiles related to pathological involvement in the temporal and frontal structures in patients with different dementia syndromes on word-list and prose memory tasks. 20 patients with Alzheimer's disease (AD), 20 with frontal variant of FTD (fvFTD), 20 with subcortical ischemic vascular dementia (SIVD), and 20 with Lewy body dementia (LBD) and 34 healthy subjects (NCs) were submitted to word-list and prose memory tasks. All groups performed similarly on both the immediate and delayed recall of the word-list. Conversely, AD patients performed worse than all the other dementia groups on the immediate prose recall. On delayed prose recall, AD patients performed worse than fvFTD and SIVD patients but similar to LBD patients. Differential scores between word-list and prose tests were minimal in the AD group and very pronounced in fvFTD and SIVD groups. The combined use of the prose and word-list tasks evidenced a "mesio-temporal" memory profile in AD patients as opposed to a "frontal" one in fvFTD and SIVD patients and a mixed profile in the LBD patients. In particular, a differential score between the two tests can be useful in differentiating AD patients from patients with other forms of dementia.

Cognitive dysfunctions in recreational and dependent cocaine users: role of attention-deficit hyperactivity disorder, craving and early age at onset

Dependent cocaine users consistently display cognitive deficits but cognitive performance of recreational cocaine users has rarely been investigated. To examine whether cognitive performance is impaired in relatively pure recreational and dependent cocaine users. The cognitive performance of recreational (n = 68) and dependent cocaine users (n = 30) was compared with the performance of stimulant-naive controls (n = 68) employing an extensive neuropsychological test battery. Moreover, the impact of attention-deficit hyperactivity disorder (ADHD) symptoms, craving and early age at onset was analysed. Dependent cocaine users display broad cognitive impairments in the domains of attention, working memory, declarative memory and executive functions. The performance of recreational cocaine users in all four domains was intermediate between that of controls and dependent users and they displayed significant deficits foremost in the domains of attention and working memory. In addition, ADHD symptoms, craving and age at onset were important modulators of cognitive function in cocaine users. Cognitive deficits occur at a recreational and non-dependent level of cocaine use. Cocaine use and ADHD seem to have mutually aggravating effects on cognitive impairment.

Representational demands modulate involvement of perirhinal cortex in face processing

The classic view holds that the medial temporal lobes (MTL) are dedicated to declarative memory functioning. Recent evidence, however, suggests that perirhinal cortex (PrC), a structure within the anterior MTL, may also play a role in perceptual discriminations when representations of complex conjunctions of features, or of gestalt-characteristics of objects must be generated. Interestingly, neuroimaging and electrophysiological recordings in nonhuman primates have also revealed a face patch in the anterior collateral sulcus with preferential responses to face stimuli in various task contexts. In the present fMRI study, we investigated the representational demands that influence PrC involvement in different types of judgments on human faces. Holding stimulus complexity constant, we independently manipulated the nature of the task and the orientation of the stimuli presented (through face inversion). Aspects of right PrC showed increased responses in a forced-choice recognition-memory and a perceptual-oddity task, as compared to a feature-search task that was included to probe visual detection of an isolated face feature. Effects of stimulus orientation in right PrC were observed when the recognition-memory condition for upright faces was compared with all other experimental conditions, including recognition-memory for inverted faces-a result that can be related to past work on the role of PrC in object unitization. Notably, both effects in right PrC paralleled activity patterns in broader networks of regions that also included the right fusiform gyrus and the amygdala, regions frequently implicated in face processing in prior research. As such, the current findings do not support the view that reference to a prior study episode clearly distinguishes the role of PrC from that of more posterior ventral visual pathway regions. They add to a growing body of evidence suggesting that the functional role of specific MTL structures may be best understood in terms of the representations that are required by the task and the stimuli at hand.

Subjective impairment after cardiac surgeries: the relevance of postoperative cognitive decline in daily living

Postoperative cognitive decline (POCD) is a frequent complication after cardiac surgeries. It remains unclear how relevant this decline in psychometric results is for daily life. The aim of the study was to assess cognitive failures, as seen by patients and close relatives, on a quantitative level. In addition to an extensive neuropsychological test battery, we interviewed 82 patients with a modified version of the self-assessment cognitive failure questionnaire (s-CFQ) and 62 close relatives (mostly spouses) with the CFQ-for-others version (f-CFQ) before and 3 months after aortic valve replacement. The questionnaires evaluate the frequency of failures in daily living related to memory, attention, action and perception. POCD occurred in all tests that had been applied to assess declarative memory functions; the mean performance dropped from baseline in these tests (P-values ranging from 0.033 and <0.001). The s-CFQ did not differ between baseline and postoperative assessment [baseline: mean 37.60, standard deviation (SD) 14.38; post: mean 36.22, SD 12.29] (t(0.05, 76) = 1.17; P = 0.246). However, the assessment by others was worse in the f-CFQ after surgery (baseline: mean 8.02, SD 4.51; post: mean 9.58, SD 6.11) (t(0.05, 61) = 2.61; P = 0.012). All changes were observed in questions related to memory and attention failures only. Higher (worse) rates in f-CFQ change scores correlated with neuropsychological change scores, namely in pictorial memory (mistakes) (r = 0.35; P = 0.003) and word fluency (correct answers) (r = -0.29; P = 0.014). Additionally, those patients with worse f-CFQ change scores (>1 SD) from baseline had clearly worse outcomes in word fluency (t(0.05, 60) = 2.53; P = 0.007) and non-verbal learning (t(0.05, 60) = 2.66; P = 0.005). The effects remained significant when controlled for depression/anxiety scores. The result demonstrates that cognitive side-effects could have a perceivable impact on daily living functions. However, slight deficits are more realized by others than by the patients themselves. Correlations between ratings by others and psychometric cognitive measures indicate that assessment by others is more reliable than self-assessment.

No effect of acute tryptophan depletion on verbal declarative memory in young persons with ADHD

Animal experiments and studies in adults have shown that the neurotransmitter serotonin (5-HT) plays an important role in learning and memory processes. However, data on this relationship in young persons are scarce, and neurodietary research in this age group is limited compared with the extensive literature on adults. Here, we aimed to explore the effects of a diminished central nervous 5-HT synthesis, which is achieved by acute tryptophan depletion (ATD) Moja-De , on memory function in young males with attention deficit hyperactivity disorder (ADHD). Twenty-two male patients with ADHD (ages 9-15 years, mean 10.95 ± 1.17 years) received ATD, thus diminishing central nervous 5-HT synthesis, and a tryptophan-balanced amino acid load (BAL) in a randomized, double-blind, within-subject, crossover design study. Approximately 1.7 h after administration of ATD/BAL, verbal declarative memory was assessed using the 'Auditory Verbal-Learning-Test' (AVLT). There were no significant effects of ATD administration on verbal declarative memory function. In this study, changes in 5-HT neurotransmission were not associated with specific aspects of verbal declarative memory in young persons with ADHD. Future studies with healthy control groups that address effects of covarying attentional processes are warranted.

Using Voxel-Based Morphometry to Examine the Relationship between Regional Brain Volumes and Memory Performance in Amnestic Mild Cognitive Impairment

Alzheimer’s disease (AD) is a slowly progressive neurodegenerative disorder, in which morphological alterations of brain tissue develop many years before the first neuropsychological and clinical changes occur. Among the first and most prominent symptoms are deficiencies of declarative memory functions. This stage of precursory symptoms to AD has been described as amnestic mild cognitive impairment (aMCI) and is discussed as a potential AD prodrome. As therapy in the later stages of AD has been shown to be of limited impact, aMCI would be the key target for early intervention. For that purpose a comprehensive neuropsychological and anatomical characterization of this group is necessary. Previous neuropsychological investigations identified tests which are highly sensitive in diagnosing aMCI and very early AD. However, the sensitivity of those neuropsychological tests to the particular structural neuropathology in aMCI remains to be specified. To this end, we investigated 25 patients with single-domain aMCI. All participants underwent extensive neuropsychological testing and anatomical scanning with structural magnetic resonance imaging. Voxel-based morphometry (VBM) was performed to identify brain regions that show a significant correlation between regional brain volume and behavioral measures of memory and executive functioning. We found that performance in a variety of mnemonic tests was directly related to the integrity of the medial temporal lobe cortex (MTLC). Moreover, impairment of memory sub-functions in aMCI might be detected earlier than overt structural damage. By this, these findings contribute to the identification of cerebral structures associated with memory deficits in aMCI.

Modulation of NGF by cortisol and the Stellate Ganglion Block – Is this the missing link between memory consolidation and PTSD?

Post-Traumatic Stress Disorder (PTSD) is a common psychiatric disorder that is often associated with intrusive memories and deficits in declarative memory function. The neurobiology of this effect is complex. The report focus is to provide an overview of systems activated during stress and consequences of the activation as well as modulation of those effects. Two systems predominate in stress and related memory processing and encoding. They are the autonomic nervous system (ANS) and hypothalamic–pituitary–adrenal axis (HPA) axis. ANS has significant effect on enhancing encoding of emotional memories, sensitization, and fear conditioning with the main neurotransmitter being norepinephrine (NE). HPA system is involved in memory regulation where cortisol (CORT), by itself and with NE, regulates memories of emotional events. Therapeutic interference with stress-related memory dysfunction has been a focus of research for some time. New focus of this research may be the HPA axis and ANS. Recent evidence demonstrates significant efficacy in prevention of PTSD by administration of CORT, as well as treatment of PTSD by utilization of Stellate Ganglion Block (SGB), which reduces NE. Both therapeutic approaches may act by a common pathway involving Nerve Growth Factor (NGF). This factor may be the “missing link” between memory consolidation and PTSD. Suppression of NGF can reduce memory effect directly or by effect on NE, leading to prevention or effective treatment of PTSD.