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White matter (WM) fiber tract differences are present in autism spectrum disorder (ASD) and could be important markers of behavior. One of the earliest phenotypic differences in ASD are language atypicalities. Although language has been linked to WM in typical development, no work has evaluated this association in early ASD. Participants came from the Infant Brain Imaging Study and included 321 infant siblings of children with ASD at high likelihood (HL) for developing ASD; 70 HL infants were later diagnosed with ASD (HL-ASD), and 251 HL infants were not diagnosed with ASD (HL-Neg). A control sample of 140 low likelihood infants not diagnosed with ASD (LL-Neg) were also included. Infants contributed expressive language, receptive language, and diffusion tensor imaging data at 6-, 12-, and 24 months. Mixed effects regression models were conducted to evaluate associations between WM and language trajectories. Trajectories of microstructural changes in the right arcuate fasciculus were associated with expressive language development. HL-ASD infants demonstrated a different developmental pattern compared to the HL-Neg and LL-Neg groups, wherein the HL-ASD group exhibited a positive association between WM fractional anisotropy and language whereas HL-Neg and LL-Neg groups showed weak or no association. No other fiber tracts demonstrated significant associations with language. In conclusion, results indicated arcuate fasciculus WM is linked to language in early toddlerhood for autistic toddlers, with the strongest associations emerging around 24 months. To our knowledge, this is the first study to evaluate associations between language and WM development during the pre-symptomatic period in ASD.

The human brain grows quickly during infancy and early childhood, but factors influencing brain maturation in this period remain poorly understood. To address this gap, we harmonized data from eight diverse cohorts, creating one of the largest pediatric neuroimaging datasets to date focused on birth to 6 years of age. We mapped the developmental trajectory of intracranial and subcortical volumes in ∼2,000 children and studied how sociodemographic factors and adverse birth outcomes influence brain structure and cognition. The amygdala was the first subcortical volume to mature, whereas the thalamus exhibited protracted development. Males had larger brain volumes than females, and children born preterm or with low birthweight showed catch-up growth with age. Socioeconomic factors exerted region- and time-specific effects. Regarding cognition, males scored lower than females; preterm birth affected all developmental areas tested, and socioeconomic factors affected visual reception and receptive language. Brain–cognition correlations revealed region-specific associations.

Objective: Previous findings of excess brain lactate and delayed end-tidal C[O.sub.2] (pC[O.sub.2]) recovery in subjects with panic disorder during hyperventilation suggested altered acid-base regulation. Two models were posited to explain these results: 1) subjects with panic disorder demonstrate greater alkalosis to hyperventilation, implicating increased lactate as directly compensatory, or 2) subjects with panic disorder demonstrate reduced or blunted alkalosis, implicating increased lactate as overly compensatory to a normal pH response. In both models, delayed pC[O.sub.2] recovery in subjects with panic disorder could reflect slower pH normalization in the recovery phase. Method: Asymptomatic medicated patients with panic disorder were studied during regulated hyperventilation. Phosphorous spectroscopy was used to measure brain pH every 2 minutes. Nine subjects with panic disorder were compared to 11 healthy subjects at baseline (five scans), during regulated hyperventilation (five scans), and across recovery (10 scans). Anxiety symptoms were assessed with standard ratings. Results: No subject had a panic attack before hyperventilation. Subjects with panic disorder had lower pC[O.sub.2] during hyperventilation and slower pC[O.sub.2] recovery across the posthyperventilation interval. Despite this different respiratory response in the panic disorder group, brain pH increases were not significantly greater during hyperventilation, nor was pH return to baseline slowed during posthyperventilation. A linear regression model derived from data of healthy subjects showed pH blunting in the panic disorder group. Conclusions: Although subjects with panic disorder had greater hypocapnea during hyperventilation, their observed pH response, not altered from comparison levels, implicated exaggerated buffering. It is suggested that increased lactate could account for these findings.

Objective: Shape differences in the caudate heads and putamen were compared between drug-naive and drug-treated patients with bipolar disorder and healthy comparison subjects by using spherical harmonic (SPHARM) techniques. On the basis of previous studies, the authors hypothesized that the drug-naive patients would exhibit shape differences of the caudate heads and putamen, especially on the right side, relative to the healthy comparison subjects, and that shape differences, relative to healthy comparison subjects, would differ between drug-naive and drug-treated patients. Method: Brain magnetic resonance images were acquired from 49 bipolar disorder patients (21 drug-naive and 28 drugtreated patients) and 37 healthy comparison subjects. Volumetric measurements were obtained, and SPHARM descriptions were used to measure between-group radius differences in the surfaces of the caudate heads and putamen. Results: Although no significant between-group volume differences were found in the striatal structures, significant shape differences in the anterior and ventral surfaces of the striatum were observed. Specifically, shape differences, more prominent for the right side, were found for drug-naive bipolar disorder patients, relative to the healthy comparison subjects, but not for drug-treated bipolar disorder subjects. Conclusions: The findings suggest that drug-naive bipolar disorder patients have shape differences of the striatum, relative to healthy comparison subjects, and that these differences may be modulated by treatment. The findings more generally demonstrate the sensitivity of the SPHARM analytic technique for detecting subtle anatomical shape differences in small brain regions in the absence of volume differences.

Objective: Pediatric populations, including those with autistic disorder or other pervasive developmental disorders, increasingly are being prescribed selective serotonin reuptake inhibitors (SSRIs). Little is known about the age-related brain pharmacokinetics of SSRIs; there is a lack of data regarding optimal dosing of medications for children. The authors used fluorine magnetic resonance spectroscopy ([sup.19]F MRS) to evaluate age effects on whole-brain concentrations of fluvoxamine and fluoxetine in children taking SSRIs. Method: Twenty-one pediatric subjects with diagnoses of autistic disorder or other pervasive developmental disorders, 6-15 years old and stabilized with a consistent dose of fluvoxamine or fluoxetine, were recruited for the study; 16 successfully completed the imaging protocol. Whole-brain drug levels in this group were compared to similarly acquired data from 28 adults. Results: A significant relationship between dose and brain drug concentration was observed for both drugs across the age range studied. Brain fluvoxamine concentration in the children was lower, consistent with a lower dose/body mass drug prescription; when brain concentration was adjusted for dose/mass, age effects were no longer significant. Brain fluoxetine concentration was similar between age groups; no significant age effects on brain fluoxetine drug levels remained after adjustment for dose/mass. Observations of brain fluoxetine bioavailability and elimination half-life also were similar between age groups. Conclusions: These findings suggest that fluvoxamine or fluoxetine prescriptions adjusted for dose/mass are an acceptable treatment approach for medicating children with autistic disorder or other pervasive developmental disorders. It must be determined whether these findings can be generalized to other pediatric populations. (Am J Psychiatry 2002; 159:755-760)

Objective: Since there is limited information concerning caffeine's metabolic effects on the human brain, the authors applied a rapid proton echo-planar spectroscopic imaging technique to dynamically measure regional brain metabolic responses to caffeine ingestion. They specifically measured changes in brain lactate due to the combined effects of caffeine's stimulation of glycolysis and reduction of cerebral blood flow. Method: Nine heavy caffeine users and nine caffeine-intolerant individuals, who had previously discontinued or substantially curtailed use of caffeinated products because of associated anxiety and discomforting physiological arousal, were studied at baseline and then during 1 hour following ingestion of caffeine citrate (10 mg/kg). To assess state-trait contributions and the effects of caffeine tolerance, five of the caffeine users were restudied after a 1- to 2-month caffeine holiday. Results: The caffeine-intolerant individuals, but not the regular caffeine users, experienced substantial psychological and physiological distress in response to caffeine ingestion. Significant increases in global and regionally specific brain lactate were observed only among the caffeine-intolerant subjects. Reexposure of the regular caffeine users to caffeine after a caffeine holiday resulted in little or no adverse clinical reaction but significant rises in brain lactate which were of a magnitude similar to that observed for the caffeine-intolerant group. Conclusions: These results provide direct evidence for the loss of caffeine tolerance in the human brain subsequent to caffeine discontinuation and suggest mechanisms for the phenomenon of caffeine intolerance other than its metabolic effects on elevating brain lactate.

Objective: The purpose of this study was to investigate the pharmacokinetics of fluvoxamine in the human brain by using fluorine-19 magnetic resonance spectroscopy (19F MRS) and to assess the relationships among fluvoxamine brain levels, fluvoxamine plasma levels, and clinical efficacy. Method: Eight subjects with DSM-IV obsessive-compulsive disorder were entered into a prospective, open-label treatment trial of fluvoxamine. 19F MRS measurements of whole brain drug and metabolite concentrations and spin-lattice ([T.sub.1]) relaxation times were performed serially in seven subjects for up to 5 months. A psychiatric determination of clinical response and a blood sample for plasma fluvoxamine measurement were obtained at each 19F MRS session. Results: The subjects achieved steady-state brain concentrations of fluvoxamine within 30 days after consistent daily dosing, as determined by stabilization of brain fluvoxamine concentrations. The mean brain-to-plasma ratio at steady state was 24 to 1. Brain fluvoxamine [T.sub.1] values from 140 to 230 msec were observed. All but one subject experienced substantial improvement in symptoms. The one nonresponder exhibited several-fold higher plasma and brain fluvoxamine levels. Conclusions: Brain fluvoxamine levels were substantially higher than plasma levels. Steady-state brain levels correlated to plasma levels but not to dose. Systematic assessment of treatment response in relation to brain or plasma fluvoxamine level was not feasible because of the marked and rapid clinical response during open-label treatment. These data suggest that fluvoxamine attains brain steady-state levels substantially faster than fluoxetine, with corresponding clinical implications.

Objective: The purpose of this study was to investigate differential effects of hyperventilation on brain lactate in patients with panic disorder and comparison subjects as a possible mechanism for explaining previous observations of an excess rise in brain lactate among panic disorder subjects during lactate infusion. Method: Seven treatment-responsive patients with panic disorder and seven healthy comparison subjects were studied with proton magnetic resonance spectroscopy to measure brain lactate during controlled, voluntary hyperventilation over a period of 20 minutes. Hyperventilation was regulated with the use of capnometry to maintain end-tidal Pc[o.sub.2] at approximately 20 mm Hg during the period of hyperventilation. Blood lactate was measured prior to and at the end of hyperventilation. Results: At baseline the two groups bad similar brain lactate levels. Panic disorder subjects exhibited significantly greater rises in brain lactate than comparison subjects in response to the same level of hyperventilation. Blood lactate levels before and after 20 minutes of hyperventilation were not significantly different between groups. Conclusions: Controlled hyperventilation increases brain lactate and does so disproportionately in subjects with panic disorder. This increase in brain lactate may result from decreased cerebral blood flow due to hypocapnia, and individuals with panic disorder may have greater sensitivity to this regulatory mechanism.

Objective: To characterize changes associated with lactate-induced panic, proton magnetic resonance spectroscopy (MRS) was used to measure brain lactate during intravenous infusion of 0.5-M sodium lactate in panic disorder patients and comparison subjects. Method: Eight panic disorder subjects, five medicated and three unmedicated, and eight healthy comparison subjects were studied at baseline, during lactate infusion (5 meq/kg over 20 minutes), and after infusion. Localized proton MRS was used to acquire averaged spectra every 5 minutes from a 27-ml sampling volume in the insular cortex and adjacent regions. Brain lactate levels, quantitatively estimated in relationship to N-acetyl aspartate, were compared to blood lactate levels. Results: The procedure was generally well tolerated; one panic subject requested early termination before lactate infusion. Significant rises in brain lactate levels occurred for all subjects during infusion. The panic patients who responded to lactate (N=3) had significantly higher brain lactate levels before, during, and after infusion than did the comparison subjects (N=8) and medicated patients who were lactate nonresponders (N=4). After infusion the panic patients with lactate-induced panic exhibited a striking dissociation between decreasing blood lactate and further increases in brain lactate levels. Conclusions: These preliminary observations indicate that brain lactate increases during a standard lactate infusion. Lactate-induced panic is associated with greater increases than in comparison subjects and with prolonged elevations in brain lactate that are decoupled from falling blood lactate levels after completion of lactate infusion. Further investigation is necessary to clarify the mechanism(s) responsible for these findings and establish whether a causal relationship to the occurrence of lactate-induced panic exists.

Objective: This study sought to determine whether dawn simulation was superior to a shorter dimmer 'placebo' dawn signal in treating winter depression. Method: In a randomized, parallel design, 22 patients with winter depression were treated with either 1 week of a 2-hour dawn simulation peaking at 250 lux or 1 week of a 30-minute dawn simulation peaking at 0.2 lux. The subjects were told that they would receive either a 'gradual' dawn or a 'rapid' dawn reaching an intensity that would be dimmer than standard bright light treatment. At the end of both the baseline week and the treatment week, subjects were assessed in a blind manner with the Hamilton Rating Scale for Depression. Analysis of covariance was used to compare the two dawn treatments. Results: The 2-hour, 250-lux dawn simulation resulted in Hamilton depression scale scores that were significantly lower than scores after the 30-minute, 0.2-lux dawn simulation. Conclusions: This study indicates that dawn simulation is an effective treatment for winter depression. (Am J Psychiatry 1993; 150:113-117)

The goal of this study is to characterize health outcomes across 3 domains—overall well-being, behavioral health, and physical health—in a large sample of autistic and non-autistic children and adolescents in the Environmental influences on Child Health Outcomes (ECHO) program.

Restricted and repetitive behaviors (RRBs), detectable by 12 months in many infants in whom autism spectrum disorder (ASD) is later diagnosed, may represent some of the earliest behavioral markers of ASD. However, brain function underlying the emergence of these key behaviors remains unknown.

Younger siblings of children with autism spectrum disorder (ASD) are themselves at increased risk for ASD and other developmental concerns. It is unclear if infants who display developmental concerns, but are unaffected by ASD, share similar or dissimilar behavioral and brain phenotypes to infants with ASD. Most individuals with ASD exhibit heterogeneous difficulties with language, and their receptive-expressive language profiles are often atypical. Yet, little is known about the neurobiology that contributes to these language difficulties.

Brain enlargement has been observed in children with autism spectrum disorder (ASD), but the timing of this phenomenon, and the relationship between ASD and the appearance of behavioural symptoms, are unknown. Retrospective head circumference and longitudinal brain volume studies of two-year olds followed up at four years of age have provided evidence that increased brain volume may emerge early in development. Studies of infants at high familial risk of autism can provide insight into the early development of autism and have shown that characteristic social deficits in ASD emerge during the latter part of the first and in the second year of life. These observations suggest that prospective brain-imaging studies of infants at high familial risk of ASD might identify early postnatal changes in brain volume that occur before an ASD diagnosis. In this prospective neuroimaging study of 106 infants at high familial risk of ASD and 42 low-risk infants, we show that hyperexpansion of the cortical surface area between 6 and 12 months of age precedes brain volume overgrowth observed between 12 and 24 months in 15 high-risk infants who were diagnosed with autism at 24 months. Brain volume overgrowth was linked to the emergence and severity of autistic social deficits. A deep-learning algorithm that primarily uses surface area information from magnetic resonance imaging of the brain of 6–12-month-old individuals predicted the diagnosis of autism in individual high-risk children at 24 months (with a positive predictive value of 81% and a sensitivity of 88%). These findings demonstrate that early brain changes occur during the period in which autistic behaviours are first emerging.

Research has shown that alcoholism and panic disorder coexist in a significant proportion of patients. Panic disorder, a common psychiatric problem, causes sudden intense periods of fearfulness and a sense of impending doom; symptoms during attacks include shortness of breath, palpitations, chest discomfort and fear of losing control. Panic disorder may lead to alcoholism; patients have reported that drinking helped them face difficult situations. In other individuals, chronic alcohol abuse may increase fearfulness and anxiety and lead to panic disorder. There is some evidence that panic attacks in alcoholics may result from alcohol withdrawal. A means of identifying persons with panic disorder is intravenous infusion of sodium lactate; patients with panic attacks are more likely to respond to lactate with psychological and physiological symptoms of panic than normal controls. The researchers tested whether response to lactate infusion was a reliable indicator of panic disorder in individuals who had already been carefully diagnosed with this condition. Twelve alcoholics with panic disorder, 10 alcoholics without it, and 16 nonalcoholics with panic disorder were included. Lactate-induced panic was observed consistently as anticipated in alcoholics and nonalcoholics with a history of panic attacks. These two groups had similar reactions to the lactate infusion, suggesting that panic disorder is similar in alcoholics and nonalcoholics. The lactate test appeared to be a useful and specific tool for identifying panic disorder. It may be particularly valuable for diagnosis in alcoholics, a group that has been difficult to diagnose by other means because of the overlap between the symptoms of panic disorder and alcoholism.

Benzodiazepine is psychotropic drug prescribed to reduce anxiety. A study of the effects of benzodiazepine withdrawal on 40 people with an existing panic attack condition was conducted. A gradual tapering off of medication was followed by an abrupt discontinuation. Medication withdrawal in victims of panic attacks has long been an observed phenomenon but comparatively little research in this area is currently available. In general, the withdrawal process involves three phases: relapse (a return to the original anxious state); rebound (an increase in the level of anxiety exceeding the original baseline condition); and withdrawal associated with the discontinuation of the drug without anxiety. Symptoms of withdrawal are known to vary with the type of medication that is used. Because of the way this study was designed, relapse and rebound stages could not be distinguished and conclusions were based upon the relative change in the status of the patients. The group was divided randomly into three subgroups and each one was given either alprazolam, diazepam (both benzodiazepines) or a placebo for six weeks. This was followed by a two-week tapering off period and then a sudden discontinuation. All subjects were measured for anxiety during these periods. At the end of the gradual reduction period, there was no significant difference in the incidence of panic attacks or in the general anxiety level of the patients. However, following the abrupt discontinuation, the patients who had been taking the alprazolam showed higher rates of generalized anxiety. A higher frequency of panic attacks, which are characterized by more intense anxiety, was not observed in any one group. The results of this study are preliminary and are limited by some of the following factors: small sample size; a wide variety of specific disorders within the patient population; different half-lives (the time required to metabolize half the substance taken) for the two benzodiazepines used. However, the findings indicated that there were more withdrawal difficulties associated with alprazolam than with diazepam. Additional study with a larger and more homogenous patient sampling and more frequent rating intervals was recommended. The relative effects of different benzodiazepines with similar half-lives should also be examined.

On July 22, 2011, Anders Breivik, a Norwegian citizen, detonated a fertilizer bomb near government buildings in Oslo, killing eight people, and then proceeded to a nearby island where the Labor Party was holding a youth camp. There, he killed 69 people before being arrested. Just before these events, he posted a “compendium” on the Web explaining his actions and encouraging others to do likewise. Much of the ensuing media coverage and trial focused on whether he was sane and whether he had a psychiatric diagnosis. One team of court-appointed psychiatrists found him to be psychotic with a diagnosis of paranoid schizophrenia and legally insane. A second team found him neither psychotic nor schizophrenic and, thus, legally sane. Their contrary opinions were not reconciled by observing his behavior in court. We discuss why experienced psychiatrists reached such fundamentally opposing diagnostic conclusions about a “home-grown” terrorist holding extreme political views.

There is disagreement about allowing propofol sedation for research magnetic resonance imaging/spectroscopy (MRI/MRS) in children. Our study is the first to provide relevant safety and efficacy data. With institutional approval, 108 research MRI/MRS procedures under propofol sedation were performed longitudinally on children at ages 3-4 years (N = 59) and 6-7 years (N = 49). Sedation parameters, physiological values, and outcome data were collected. Success rate for acquisition of satisfactory quality MRI/MRS during propofol sedation was compared with that in typically developing, age-matched sleeping children. Only 5 minor events (2 with need to insert an oral airway, 2 with premature termination of study, 1 with bradycardia not requiring treatment) and no major events occurred. These safety/efficacy data are equal to or better than previously reported with propofol for clinically indicated procedures. A high percentage of parents of children participating in MRI/MRS studies at 3-4 years of age returned with their child at 6-7 years of age, and longitudinal follow-up was not adversely impacted by their child's experience with sedation. The success rate of data acquisition was significantly higher during propofol sedation (98%) than during late-night sleep studies in typically developing children (30%-50%). We conclude that propofol sedation for research MRI/MRS is safe and effective when children of appropriate ASA class are selected, supplemental oxygen is delivered, and sedation and monitoring are done by an experienced anesthesiologist.

The present study explored the correlation between lactate as detected by MR spectroscopy (MRS) and blood oxygenation level dependent (BOLD) responses in male children during auditory‐based language tasks. All subjects (N= 8) participated in one proton echo planar spectroscopic imaging (PEPSI) and one functional magnetic resonance imaging (fMRI) session that required phonological and lexical judgments to aurally presented stimuli. Valid PEPSI data was limited in the frontal areas of the brain due to the magnetic susceptibility of the eye orbits and frontal sinuses. Findings from the remainder of the brain indicate that subjects show a significant consistency across imaging techniques in the left temporal area during the lexical task, but not in any other measurable area or during the phonological task. Magn Reson Med 45:217–225, 2001. © 2001 Wiley‐Liss, Inc.

Caffeine and nicotine are the most common psychostimulant drugs used worldwide. Structural neuroimaging findings associated with caffeine and nicotine consumption are limited and primarily reflect the putative relationship between smoking and white matter hyperintensities (WMH), a finding that warrants further appraisal of its clinical implications. The application of newer brain imaging modalities that measure subtle haemodynamic changes or tissue-based chemistry in order to better elucidate brain functional processes, including mechanisms underlying addiction to nicotine and caffeine and the brain functional consequences, provide intriguing findings. Potential influences of caffeine and nicotine on the functional contrast, or metabolic response, to neural activation also necessitates the careful appraisal of the effects that these commonly used drugs may have on the results of functional imaging.

A randomized, double-blind, placebo-controlled, parallel-group study was conducted to evaluate the efficacy and safety of gabapentin in relieving the symptoms of panic disorder. One hundred three patients were randomly assigned to receive double-blind treatment with either gabapentin (dosed flexibly between 600 and 3,600 mg/day) or placebo for 8 weeks. No overall drug/placebo difference was observed in scores on the Panic and Agoraphobia Scale (PAS) (p= 0.606). A post hoc analysis was used to evaluate the more severely ill patients as defined by the primary outcome measure (PAS score ≥ 20). In this population, the gabapentin-treated patients showed significant improvement in the PAS change score (p= 0.04). In patients with a PAS score of 20 or greater, women showed a greater response than men regardless of treatment. Adverse events were consistent with the known side effect profile of gabapentin and included somnolence, headache, and dizziness. One patient experienced a serious adverse event during the study. No deaths were reported. The results of this study suggest that gabapentin may have anxiolytic effects in more severely ill patients with panic disorder.

AbstractA summary of the Third International Obsessive Compulsive Disorder Conference proceedings on neuroimaging research and neurocircuitry models of obsessive-compulsive disorder (OCD) is presented. This survey of recent and ongoing research indicates that a wide range of modern techniques and experimental strategies are being employed in a complementary fashion to enhance our understanding of OCD. Imaging studies in animal models of OCD are helping to elaborate relevant normal anatomy and neuro-chemistry. Functional imaging methods are being employed in conjunction with behavioral, pharmacologic, and cognitive challenge paradigms. Magnetic resonance spectroscopy as well as radiotracer methods are being utilized to measure neurochemical and neuropharmacologic indices in OCD. Transcranial magnetic stimulation has emerged as a tool for probing neurocircuitry that may also have therapeutic potential. Experimental designs and data-analytic methods are evolving to help elucidate the pathophysiology of OCD and related disorders, delineate neurobiologically meaningful subtypes of OCD, and identify potential predictors of treatment response. Collectively, these efforts promise important advances as we approach the new millennium.

Improved data acquisition and processing strategies for blood oxygenation level‐dependent (BOLD)‐contrast functional magnetic resonance imaging (fMRI), which enhance the functional contrast‐to‐noise ratio (CNR) by sampling multiple echo times in a single shot, are described. The dependence of the CNR on T2*, the image encoding time, and the number of sampled echo times are investigated for exponential fitting, echo summation, weighted echo summation, and averaging of correlation maps obtained at different echo times. The method is validated in vivo using visual stimulation and turbo proton echoplanar spectroscopic imaging (turbo‐PEPSI), a new single‐shot multi‐slice MR spectroscopic imaging technique, which acquires up to 12 consecutive echoplanar images with echo times ranging from 12 to 213 msec. Quantitative T2*‐mapping significantly increases the measured extent of activation and the mean correlation coefficient compared with conventional echoplanar imaging. The sensitivity gain with echo summation, which is computationally efficient provides similar sensitivity as fitting. For all data processing methods sensitivity is optimum when echo times up to 3.2 T2* are sampled. This methodology has implications for comparing functional sensitivity at different magnetic field strengths and between brain regions with different magnetic field inhomogeneities. Magn Reson Med 42:87–97, 1999. © 1999 Wiley‐Liss, Inc.

A new rapid spectroscopic imaging technique with improved sensitivity and lipid suppression, referred to as Proton Echo Planar Spectroscopic Imaging (PEPSI), has been developed to measure the 2‐dimensional distribution of brain lactate increases during hyperventilation on a conventional clincal scanner equipped with a head surface coil phased array. PEPSI images (nominal voxel size: 1.125 cm3) in five healthy subjects from an axial section approximately 20 mm inferior to the intercommissural line were obtained during an 8.5‐min baseline period of normocapnia and during the final 8.5 min of a 10‐min period of capnometry‐controlled hyperventilation (end‐tidal PCO2of 20 mmHg). The lactate/N‐acetyl aspartate signal increased significantly from baseline during hyperventilation for the insular cortex, temporal cortex, and occipital regions of both the right and left hemispheres, but not in the basal ganglia. Regional or hemispheric right‐to‐left differences were not found. The study extends previous work using single‐voxel MR spectroscopy to dynamically study hyperventilation effects on brain metabolism.

Recently developed biosensor technology, which allows near real-time measurement in situ of gas tension (pCO2and pO2) and of pH, was applied to arterial blood, cerebrospinal fluid (CSF), and brain parenchyma during intravenous lactate infusion in monkeys. Comparison of simultaneous biosensor measurements and discrete arterial blood sampling for traditional blood gas analyses indicated a high level of correlation for pCO2, pO2, and pH. Arterial pO2and pH values were significantly higher and pCO2significantly lower than corresponding CSF and brain parenchyma values at baseline, during and following lactate infusion. There was a divergence between arterial and brain parenchyma pH and pO2measurements. Lactate infusion was associated with progressive arterial pH rises, consistent with the production of a metabolic alkalosis. Cerebrospinal fluid pCO2remained unchanged during and following lactate infusion. Brain parenchyma exhibited a complex pattern of response characterized by a trend for pO2and pH to decrease during lactate infusion, which reversed following completion of the infusion. These observations are suggestive of a transient hypoxia from decreased cerebral blood flow and/or reduced oxyhemoglobin dissociation during lactate infusion, but verification of these results is required.

Functional brain imaging of 6-month-old infants with a high familial risk for autism predicts a diagnosis of autism at 24 months of age.