Nancy B. Rawlings

Mental training enhances attentional stability: neural and behavioral evidence.

The capacity to stabilize the content of attention over time varies among individuals, and its impairment is a hallmark of several mental illnesses. Impairments in sustained attention in patients with attention disorders have been associated with increased trial-to-trial variability in reaction time and event-related potential deficits during attention tasks. At present, it is unclear whether the ability to sustain attention and its underlying brain circuitry are transformable through training. Here, we show, with dichotic listening task performance and electroencephalography, that training attention, as cultivated by meditation, can improve the ability to sustain attention. Three months of intensive meditation training reduced variability in attentional processing of target tones, as indicated by both enhanced theta-band phase consistency of oscillatory neural responses over anterior brain areas and reduced reaction time variability. Furthermore, those individuals who showed the greatest increase in neural response consistency showed the largest decrease in behavioral response variability. Notably, we also observed reduced variability in neural processing, in particular in low-frequency bands, regardless of whether the deviant tone was attended or unattended. Focused attention meditation may thus affect both distracter and target processing, perhaps by enhancing entrainment of neuronal oscillations to sensory input rhythms, a mechanism important for controlling the content of attention. These novel findings highlight the mechanisms underlying focused attention meditation and support the notion that mental training can significantly affect attention and brain function.

d-Amino acid oxidase and serine racemase in human brain: normal distribution and altered expression in schizophrenia.

The N‐methyl‐d‐aspartate receptor co‐agonist d‐serine is synthesized by serine racemase and degraded by d‐amino acid oxidase. Both d‐serine and its metabolizing enzymes are implicated in N‐methyl‐d‐aspartate receptor hypofunction thought to occur in schizophrenia. We studied d‐amino acid oxidase and serine racemase immunohistochemically in several brain regions and compared their immunoreactivity and their mRNA levels in the cerebellum and dorsolateral prefrontal cortex in schizophrenia. d‐Amino acid oxidase immunoreactivity was abundant in glia, especially Bergmann glia, of the cerebellum, whereas in prefrontal cortex, hippocampus and substantia nigra, it was predominantly neuronal. Serine racemase was principally glial in all regions examined and demonstrated prominent white matter staining. In schizophrenia, d‐amino acid oxidase mRNA was increased in the cerebellum, and as a trend for protein. Serine racemase was increased in schizophrenia in the dorsolateral prefrontal cortex but not in cerebellum, while serine racemase mRNA was unchanged in both regions. Administration of haloperidol to rats did not significantly affect serine racemase or d‐amino acid oxidase levels. These findings establish the major cell types wherein serine racemase and d‐amino acid oxidase are expressed in human brain and provide some support for aberrant d‐serine metabolism in schizophrenia. However, they raise further questions as to the roles of d‐amino acid oxidase and serine racemase in both physiological and pathophysiological processes in the brain.

Multi-modal characterization of rapid anterior hippocampal volume increase associated with aerobic exercise.

The hippocampus has been shown to demonstrate a remarkable degree of plasticity in response to a variety of tasks and experiences. For example, the size of the human hippocampus has been shown to increase in response to aerobic exercise. However, it is currently unknown what underlies these changes. Here we scanned sedentary, young to middle-aged human adults before and after a six-week exercise intervention using nine different neuroimaging measures of brain structure, vasculature, and diffusion. We then tested two different hypotheses regarding the nature of the underlying changes in the tissue. Surprisingly, we found no evidence of a vascular change as has been previously reported. Rather, the pattern of changes is better explained by an increase in myelination. Finally, we show that hippocampal volume increase is temporary, returning to baseline after an additional six weeks without aerobic exercise. This is the first demonstration of a change in hippocampal volume in early to middle adulthood suggesting that hippocampal volume is modulated by aerobic exercise throughout the lifespan rather than only in the presence of age related atrophy. It is also the first demonstration of hippocampal volume change over a period of only six weeks, suggesting that gross morphometric hippocampal plasticity occurs faster than previously thought.

Reduced sensitivity to both positive and negative reinforcement in mice over-expressing the 5-hydroxytryptamine transporter.

The 5‐hydroxytryptamine (5‐HT) transporter (5‐HTT) is believed to play a key role in both normal and pathological psychological states. Much previous data suggest that the s allele of the polymorphic regulatory region of the 5‐HTT gene promoter is associated with reduced 5‐HTT expression and vulnerability to psychiatric disorders, including anxiety and depression. In comparison, the l allele, which increases 5‐HTT expression, is generally considered protective. However, recent data link this allele to both abnormal 5‐HT signalling and psychopathic traits. Here, we studied the processing of aversive and rewarding cues in transgenic mice that over‐express the 5‐HTT (5‐HTTOE mice). Compared with wild‐type mice, 5‐HTTOE mice froze less in response to both a tone that had previously been paired with footshock, and the conditioning context. In addition, on a decision‐making T‐maze task, 5‐HTTOE mice displayed reduced preference for a larger, delayed reward and increased preference for a smaller, immediate reward, suggesting increased impulsiveness compared with wild‐type mice. However, further inspection of the data revealed that 5‐HTTOE mice displayed a relative insensitivity to reward magnitude, irrespective of delay. In contrast, 5‐HTTOE mice appeared normal on tests of spatial working and reference memory, which required an absolute choice between options associated with either reward or no reward. Overall, the present findings suggest that 5‐HTT over‐expression results in a reduced sensitivity to both positive and negative reinforcers. Thus, these data show that increased 5‐HTT expression has some maladaptive effects, supporting recent suggestions that l allele homozygosity may be a potential risk factor for disabling psychiatric traits.

Does agomelatine block 5-HT2C receptors in humans?

receptor antagonist properties to healthy volunteersproduces reliable increases in slow wave sleep (SWS) in thepolysomnogram (see Sharpley et al. 1994; Sharpley andCowen 1995). The aim of the present study was to test thehypothesis that agomelatine would also increase SWS inhumans.We studied 15 healthy subjects (eight female, sevenmale; mean age 25.9 years, range 19–47 years) who weredetermined by clinical interview (non-patient version of theStructured Clinical Interview for DSM-IV) to have nocurrent history of psychiatric disorder or sleep disorder andwho were not taking any other medication. Each subjecttook matching capsules of placebo and agomelatine(25 mg) once, orally, 30 min before retiring to sleep in adouble blind, balanced order, crossover design with a 7- to14-day washout period between each sleep polysomno-gram. Subjective ratings of sleep (on a five-point scale) andside effects (on a four-point scale) were elicited themorning after each sleep study.On each study night, polysomnograms were recorded aseach participant slept at home, using the Embla A10 digitaldata recording system (Medcare, Broomfield, CO, USA).Participants retired and rose at their usual time, and this waskept constant for all study nights and all preceding nights.Polysomnography involved a standard montage: four electro-encephalogram channels (C3/A2, C4/A1, O1/A2, O2/A1),two electro-oculogram channels, and a submentalis electro-myogram. Polysomnograms were staged in 30-s epochs usingthe Embla diagnostic software, Somnologica Studio. Thissoftware provides measures for all aspects of sleep architec-ture according to standard criteria. In addition, the polysomno-grams were edited by an experienced sleep physiologist blindto treatment status. The polysomnograms of two participantswere excluded due to technical difficulties. However, theirsubjective ratings were available and were included. Differ-ences between the pairs of sleep nights were assessed usingStudent’spairedt test (two-tailed).Agomelatine produced no change in any polysomno-graphic parameter including SWS (Table 1). Separate exam-ination of sequential cycles of SWS also failed to reveal anyeffect of agomelatine (data not shown). Following agomela-tine, participants rated their sleep quality as improved, butthey also experienced more nausea (Table 1).Our findings suggest that initiation of a standard clinicaldose of agomelatine does not cause functional blockade ofbrain 5-HT

An Ultra-High Field Magnetic Resonance Spectroscopy Study of Post Exercise Lactate, Glutamate and Glutamine Change in the Human Brain

During strenuous exercise there is a progressive increase in lactate uptake and metabolism into the brain as workload and plasma lactate levels increase. Although it is now widely accepted that the brain can metabolize lactate, few studies have directly measured brain lactate following vigorous exercise. Here, we used ultra-high field magnetic resonance spectroscopy of the brain to obtain static measures of brain lactate, as well as brain glutamate and glutamine after vigorous exercise. The aims of our experiment were to (a) track the changes in brain lactate following recovery from exercise, and (b) to simultaneously measure the signals from brain glutamate and glutamine. The results of our experiment showed that vigorous exercise resulted in a significant increase in brain lactate. Furthermore, both glutamate and glutamine were successfully resolved, and as expected, although contrary to some previous reports, we did not observe any significant change in either amino acid after exercise. We did however observe a negative correlation between glutamate and a measure of fitness. These results support the hypothesis that peripherally derived lactate is taken up by the brain when available. Our data additionally highlight the potential of ultra-high field MRS as a non-invasive way of measuring multiple brain metabolite changes with exercise.