Drugs and human memory (part 2). Clinical, theoretical, and methodologic issues.

Individual differences in emotion regulation and hemispheric metabolic asymmetry

Neural Correlates of Perceptual/Semantic Encoding and Implicit/Explicit Retrieval: An fMRI Study T. Park (tpark@chonnam.ac.kr) Department of Psychology, Chonnam National University Kwangju 500-757, Republic of Korea The important distinction between implicit and explicit memory tests is based on intentional effort and conscious recollection experience during retrieval process (Schacter, 1987), which have been suggested to be associated with increased activity in prefrontal and medial temporal regions, respectively (Schacter & Buckner, 1998). The present study investigated brain areas activated during tasks involving implicit and explicit memory retrieval, and examined neural correlates of conscious recollection and intentional effort during memory retrieval. Methods Whole-brain functional MRI was used to examine 8 subjects during retrieval in a block-designed fMRI experiment (Fig. 1). Two incidental study conditions were manipulated: Semantic and perceptual word encoding conditions. This manipulation of level of processing (LoP) was expected to yield two retrieval conditions that differed with regard to intentional retrieval effort and successful conscious recollection: Semantic encoding yielding low level of retrieval effort with high level of retrieval success and perceptual encoding yielding high level of effort with low level of retrieval success. After studying, word fragment completion (WFC) task was presented and then cued recall (CR) task was presented with word fragment cues. PER 30S SEM 30S 30S PER 30S 30S UNS PER SEM 30S SEM 30S 30S 30S UNS PER SEM 30S 30S 30S 30S 30S 30S 30S 30S 30S Fig. 1. A schematic illustration of study (above) and retrieval (below) paradigm. Critical study blocks (Semantic Encoding and Perceptual Encoding) were 30-s long separated by 30-s blocks of fixation (+). Critical retrieval blocks (Unstudied, Perceptually studied, Semantically studied) were also 30-s long separated by 30-s blocks of fixation in each of WFC and CR tasks. Results During explicit retrieval (CR) of the semantically encoded words, right inferior frontal regions (Brodman Areas 45, 47) were activated but right anterior frontal regions (BA 10) were deactivated. These results suggest different roles of different prefrontal regions during explicit (episodic) memory retrieval: BA 45/47 involved in conscious recollection and BA 10 in intentional effort (McIntosh et al., 1997). Also, parahippocampal gyrus was activated during explicit retrieval of the semantically encoded words, and this result supports the idea that medial temporal lobe is a neural correlate of conscious retrieval success. During implicit retrieval (WFC), occipital lobe (BA 17, 18 including fusiform gyrus) showed reduced activation when word fragments were primed, and this result supports the view that posterior areas are neural correlates of perceptual priming. Unexpectedly, right parahippocampal gyrus showed increased activation during implicit retrieval of the semantically encoded words. This result suggests that LoP effects which were often observed in studies of implicit memory retrieval could be the result of involuntary recollection (explicit contamination). Acknowledgements This research was supported as a Brain Neuroinformatics Research Program sponsored by Korean Ministry of Science and Technology. References McIntosh, A. R., Nyberg, L., Bookstein, F. L., & Tulving, E. (1997). Differential functional connectivity of prefrontal and medial temporal cortices during episodic memory retrieval. Human Brain Mapping, 5, 323-327. Schacter, D. L. (1987). Implicit memory: History and current status. Journal of Experimental Psychology: Learning, Memory, and Cognition, 13, 501-518. Schacter, D. L., & Buckner, R. L. (1998). On the relations among priming, conscious recollection, and intentional retrieval: Evidence from neuroimaging research. Neurobiology of Learning and Memory, 70, 284-303.

Emotional Reactivity in Posttraumatic Stress Disorder:Behavioural and Neurobiological Correlates of Underlying Mechanisms and the Role of Emotional Memory Modification

Positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) have been extensively used to explore the functional neuroanatomy of cognitive functions. Here we review 275 PET and fMRI studies of attention (sustained, selective, Stroop, orientation, divided), perception (object, face, space/motion, smell), imagery (object, space/motion), language (written/spoken word recognition, spoken/no spoken response), working memory (verbal/numeric, object, spatial, problem solving), semantic memory retrieval (categorization, generation), episodic memory encoding (verbal, object, spatial), episodic memory retrieval (verbal, nonverbal, success, effort, mode, context), priming (perceptual, conceptual), and procedural memory (conditioning, motor, and nonmotor skill learning). To identify consistent activation patterns associated with these cognitive operations, data from 412 contrasts were summarized at the level of cortical Brodmann's areas, insula, thalamus, medial-temporal lobe (including hippocampus), basal ganglia, and cerebellum. For perception and imagery, activation patterns included primary and secondary regions in the dorsal and ventral pathways. For attention and working memory, activations were usually found in prefrontal and parietal regions. For language and semantic memory retrieval, typical regions included left prefrontal and temporal regions. For episodic memory encoding, consistently activated regions included left prefrontal and medial temporal regions. For episodic memory retrieval, activation patterns included prefrontal, medial temporal, and posterior midline regions. For priming, deactivations in prefrontal (conceptual) or extrastriate (perceptual) regions were consistently seen. For procedural memory, activations were found in motor as well as in non-motor brain areas. Analysis of regional activations across cognitive domains suggested that several brain regions, including the cerebellum, are engaged by a variety of cognitive challenges. These observations are discussed in relation to functional specialization as well as functional integration.

Imaging the mind

Gastrointestinal (GI) peptides can increase or decrease blood flow in addition to their actions on digestive functions, such as GI motility, intestinal absorption, and gastric and pancreatic secretions. Their vasoactive potency (i.e., the dose required to produce vasoactivity) may differ from their potency to induce changes in digestive functions and, therefore, the respective potencies should be compared. The relative potency of some chemicals on GI motility and blood flow, and the relationship between these two variables, have been summarized (Chou 1989). Administration of a peptide often produces concomitant changes in a digestive function, local oxidative metabolism, and local blood flow. A change in the tissue activity and metabolism can cause changes in local blood flow, and a change in blood flow can influence tissue activity. One should determine which aspect is the cause and which is the result. Another issue to be considered is whether or not the digestive and vascular actions of a peptide are physiological. Physiologically, the GI peptides are released following a meal to regulate digestive functions and local blood flow. In order to be a physiological peptide, the postprandial tissue or blood concentrations must be sufficient to produce vasoactivity. This topic has been discussed previously by comparing the minimal local blood concentration required to produce vasodilation with that achieved following a meal (Chou and Kvietys 1981; Chou et al. 1984).

Decades of research have highlighted the importance of lateral parietal cortex (LPC) across a myriad of cognitive domains. Yet, the underlying function of LPC remains unclear. Two domains that have emphasized LPC involvement are semantic memory and episodic memory retrieval. From each domain, sophisticated functional models have been proposed, as well as the more domain-general assumption that LPC is engaged by any form of internally directed cognition (episodic/semantic retrieval being examples). Here we used a combination of functional magnetic resonance imaging, functional connectivity, and diffusion tensor imaging white-matter connectivity to show that (i) ventral LPC (angular gyrus [AG]) was positively engaged during episodic retrieval but disengaged during semantic memory retrieval and (ii) activity negatively varied with task difficulty in the semantic task whereas episodic activation was independent of difficulty. In contrast, dorsal LPC (intraparietal sulcus) showed domain general activation that was positively correlated with task difficulty. Finally, (iii) a dorsal–ventral and anterior–posterior gradient of functional and structural connectivity was found across the AG (e.g. mid-AG connected with episodic retrieval). We propose a unifying model in which LPC as a whole might share a common underlying neurocomputation (multimodal buffering) with variations in the emergent cognitive functions across subregions arising from differences in the underlying connectivity.

The aim of this randomized controlled crossover study was to investigate the effect of a bout of unaccustomed eccentric exercise (ECC) followed by a consecutive bout of the same intensity on local muscle blood flow, amplitude, and frequency of the electromyographic (EMG) signal from the exercised tibialis anterior muscle. Sixteen healthy male participants (age, 25.7 (0.6) years; body mass index 24.8 (1) kg·m(-2) participated in this study. Two identical bouts of high-intensity ECC were performed on the tibialis anterior muscle 7 days apart. Control sessions involving no exercise were performed 4 weeks either before or after the exercise sessions. Changes in local total blood flow [ΔtHb], EMG root mean square, and median power frequency were recorded during isometric maximum voluntary contraction of ankle dorsiflexion. Measurements were performed before, immediately after, and the day after both ECCs (ECC1 and ECC2). The participants rested quietly in a chair in the control session. Eccentric exercise 1 led to a significant decrease in [ΔtHb] on the day after (p ≤ 0.05), whereas ECC2 did not. Median power frequency decreased significantly in ECC2 compared with ECC1 (p < 0.01). Root mean square was unchanged in all the instants. The present study showed that adaptation is depicted in the local muscle blood flow and the frequency contents of the EMG after an unaccustomed ECC inducing muscle soreness. These alterations provide a potential mechanism for a rapid adaptation, which decreases susceptibility of the muscle to develop further soreness in the subsequent ECC bout.

Editorial I: Effect site: who needs it?

Episodic memory retrieval is fundamental for daily activities of humans and animals. Muscarinic cholinergic signaling is important for memory functioning and shows gender-dependent response in episodic memory retrieval. Dopamine D2 receptors influence memory formation and retrieval by influencing cholinergic signaling in the brain. This study aimed to determine the gender-dependent effects of D2 and muscarinic activity on memory retrieval. Male and female mice were trained for Morris water maze test and contextual fear conditioning. Memory retrieval was assessed following sub-chronic treatment (for 5days) with D2 antagonist (risperidone 2.5mg/kg) alone or in combination with scopolamine (1mg/kg) or donepezil (1mg/kg). Open field test was performed prior to the retrieval test to evaluate effects of risperidone treatment on locomotor activity and exploratory behavior. Risperidone co-treatment with donepezil impaired spatial memory retrieval in males only. Muscarinic and D2 simultaneous antagonism tend to impair fear retrieval in males but significantly enhanced retrieval of fear memories in female mice. These results suggest that D2 signaling influence muscarinic receptor activity during memory retrieval in gender-dependent manner.

Synergic action of nitric oxide (NO) and prostaglandins (PG) in the regulation of muscle blood flow during exercise has been demonstrated. In the present study, we investigated whether these vasodilators also regulate local blood flow, flow heterogeneity, and glucose uptake within the exercising skeletal muscle. Skeletal muscle blood flow was measured in seven healthy young men using near-infrared spectroscopy and indocyanine green and muscle glucose uptake using positron emission tomography and 2-fluoro-2-deoxy-D-[(18)F]glucose without and with local blockade of NO and PG at rest and during one-legged dynamic knee-extension exercise. Local blockade was produced by infusing nitro-L-arginine methyl ester and indomethacin directly in the muscle via a microdialysis catheter. Blood flow and glucose uptake were measured in the region of blockade and in two additional regions of vastus lateralis muscle 1 and 4 cm away from the infusion of blockers. Local blockade during exercise at 25 and 40 watts significantly decreased blood flow in the infusion region and in the region 1 cm away from the site of infusion but not in the region 4 cm away. During exercise, muscle glucose uptake did not show any regional differences in response to blockade. These results show that NO and PG synergistically contribute to the local regulation of blood flow in skeletal muscle independently of muscle glucose uptake in healthy young men. Thus these vasodilators can play a role in regulating microvascular blood flow in localized regions of vastus lateralis muscle but do not influence regional glucose uptake. The findings suggest that local substrate uptake in skeletal muscle can be regulated independently of regional changes in blood flow.

Stimulus-driven incidental episodic retrieval involves activation of the left posterior parietal cortex

ObjectiveAntihistamines often have sedative side effects. This was the first study to measure regional cerebral glucose (energy) consumption and hemodynamic responses in young adults during cognitive tests after antihistamine administration.MethodsIn this double‐blind, placebo‐controlled, three‐way crossover study, 18 healthy young Japanese men received single doses of levocetirizine 5 mg and diphenhydramine 50 mg at intervals of at least six days. Subjective feeling, task performances, and brain activity were evaluated during three cognitive tests (word fluency, two‐back, and Stroop). Regional cerebral glucose consumption changes were measured using positron emission tomography with [18F]fluorodeoxyglucose. Regional hemodynamic responses were measured using near‐infrared spectroscopy.ResultsEnergy consumption in prefrontal regions was significantly increased after antihistamine administration, especially diphenhydramine, whereas prefrontal hemodynamic responses, evaluated with oxygenated hemoglobin levels, were significantly lower with diphenhydramine treatment. Stroop test accuracy was significantly impaired by diphenhydramine, but not by levocetirizine. There was no significant difference in subjective sleepiness.ConclusionsPhysiological “coupling” between metabolism and perfusion in the healthy human brain may not be maintained under pharmacological influence due to antihistamines. This uncoupling may be caused by a combination of increased energy demands in the prefrontal regions and suppression of vascular permeability in brain capillaries after antihistamine treatment. Further research is needed to validate this hypothesis.

Revealing Brain Activity and White Matter Structure Using Functional and Diffusion-Weighted Magnetic Resonance Imaging

The effect of hemorrhagic hypotension on total and local renal blood flow in the rat.