Proteomic Markers of Non-functional Overreaching During the Race Across America (RAAM): A Case Study.

In a previous study, proteomics procedures identified blood proteins as potential overreaching and overtraining biomarkers, and a targeted proteomics panel of 21 proteins was developed. PURPOSE: To measure targeted blood protein changes in an ultraendurance cyclist competing in RAAM. METHODS: The athlete underwent testing 4-week pre-RAAM and 4-day post-RAAM to determine body composition and aerobic capacity. During RAAM training distress score (TDS) and body mass were measured daily. Power output and heart rate (HR) were measured during cycling. Blood sampling for proteomic analysis occurred 4 weeks, 24, and 2 h before the start, twice per day of the race, and after 1 and 4 days recovery. RESULTS: The athlete completed the 4941 km race in 10.1 days at a speed of 24.5 km/h with 20 total hours of sleep. TDS was very low, 1, pre-RAAM and increased to very high, 47, at the finish. Post-RAAM maximal aerobic capacity and HR were 6.3 and 5.7% lower (61.6 vs. 57.5 mL.kg-1.min-1 and 192 bpm vs. 181 bpm). Body composition did not change. The change in blood proteins was calculated using pre-race samples and samples collected on days 8, 9, and recovery day 1. The blood proteins with the largest increase were complement component C7 (359%), complement C4-B (231%), serum amyloid A-4 protein (210%), inter-alpha-trypsin inhibitor heavy chain H4 (191%), and alpha-1-antitrypsin (188%). CONCLUSION: The RAAM athlete exhibited non-functional overreaching symptoms including increased training distress and decreased work capacity. Proteomic analysis indicated large increases for immune-related proteins involved with complement activation and the acute phase response, which could be useful biomarkers for non-functional overreaching.

The functional anatomy of suggested limb paralysis.

Suggestions of limb paralysis in highly hypnotically suggestible subjects have been employed to successfully model conversion disorders, revealing similar patterns of brain activation associated with attempted movement of the affected limb. However, previous studies differ with regard to the executive regions involved during involuntary inhibition of the affected limb. This difference may have arisen as previous studies did not control for differences in hypnosis depth between conditions and/or include subjective measures to explore the experience of suggested paralysis. In the current study we employed functional magnetic resonance imaging (fMRI) to examine the functional anatomy of left and right upper limb movements in eight healthy subjects selected for high hypnotic suggestibility during (i) hypnosis (NORMAL) and (ii) attempted movement following additional left upper limb paralysis suggestions (PARALYSIS). Contrast of left upper limb motor function during NORMAL relative to PARALYSIS conditions revealed greater activation of contralateral M1/S1 and ipsilateral cerebellum, consistent with the engagement of these regions in the completion of movements. By contrast, two significant observations were noted in PARALYSIS relative to NORMAL conditions. In conjunction with reports of attempts to move the paralysed limb, greater supplementary motor area (SMA) activation was observed, a finding consistent with the role of SMA in motor intention and planning. The anterior cingulate cortex (ACC, BA 24) was also significantly more active in PARALYSIS relative to NORMAL conditions - suggesting that ACC (BA 24) may be implicated in involuntary, as well as voluntary inhibition of prepotent motor responses.

Modulating the default mode network using hypnosis.

Debate regarding the neural basis of the hypnotic state continues, but a recent hypothesis suggests that it may produce alterations in the default mode network (DMN). DMN describes a network of brain regions more active during low-demand compared to high-demand task conditions and has been linked to processes such as task-independent thinking, episodic memory, semantic processing, and self-awareness. However, the experiential and cognitive correlates of DMN remain difficult to investigate directly. Using hypnosis as a means of altering the resting ("default") state in conjunction with subjective measures and brain imaging, the authors found that the state of attentional absorption following a hypnotic induction was associated with reduced activity in DMN and increased activity in prefrontal attentional systems, under invariant conditions of passive visual stimulation. The findings that hypnosis and spontaneous conceptual thought at rest were subjectively and neurally distinctive are also relevant to understanding hypnosis itself.

Increased cerebral perfusion in adult attention deficit hyperactivity disorder is normalised by stimulant treatment: a non-invasive MRI pilot study.

The neurobiological basis for attention deficit hyperactivity disorder (ADHD) has not yet been fully established, although there is a growing body of evidence pointing to functional and structural abnormalities involving the basal ganglia, cerebellum, and regions of frontal grey matter. The purpose of this study was to investigate regional cerebral perfusion in adults with ADHD and age-matched control subjects, and to assess the perfusion response to stimulant treatment in the ADHD group using a non-invasive magnetic resonance perfusion imaging technique. Whole-brain cerebral perfusion images were acquired from nine right-handed male patients with ADHD and eleven age-matched control subjects using a continuous arterial spin labelling (CASL) technique. The ADHD group was assessed once on their normal treatment and once after withdrawing from treatment for at least one week. An automated voxel-based analysis was used to identify regions where the cerebral perfusion differed significantly between the ADHD and control groups, and where the perfusion altered significantly with stimulant treatment. Regional cerebral perfusion was increased in the ADHD group in the left caudate nucleus, frontal and parietal regions. Psychomotor stimulant treatment acted to normalise perfusion in frontal cortex and the caudate nucleus with additional decreases in parietal and parahippocampal regions. These findings highlight the potential sensitivity of non-invasive perfusion MRI techniques like CASL in the evaluation of perfusion differences due to illness and medication treatment, and provide further evidence that persistence of ADHD symptomatology into adulthood is accompanied by abnormalities in frontal and striatal brain regions.

Planning ability in adults with attention-deficit/hyperactivity disorder.

Planning ability was investigated in 26 patients diagnosed with attention-deficit/hyperactivity disorder in adulthood and in 27 control participants, with groups matched for age, predicted IQ, and social class. They were tested using the 3-dimensional computerized Tower of London Test (Morris, Ahmed, Syed, & Toone, 1993; Morris, Rushe, Woodruffe, & Murray, 1995), which measures planning latencies as well as accuracy, with problems increasing in graded difficulty. For the control group, planning latencies increased systematically with task difficulty, with the participants slowing their initial responses to ensure accuracy. For those with attention-deficit/hyperactivity disorder, there was no increase in planning time and a corresponding diminution in accuracy on the most difficult problems. This pattern of impairment is interpreted as resulting from failure to inhibit responses when confronted with problem solving, leading to reduced planning activity.

Task-specific hypoactivation in prefrontal and temporoparietal brain regions during motor inhibition and task switching in medication-naive children and adolescents with attention deficit hyperactivity disorder.

OBJECTIVE: A relatively small number of functional imaging studies of attention deficit hyperactivity disorder (ADHD) have shown abnormal prefrontal and striatal brain activation during tasks of motor response inhibition. However, the potential confound of previous medication exposure has not yet been addressed, and no functional imaging study exists to date on medication-naive children and adolescents with ADHD. The aim of this study was to investigate the neural substrates of a range of motor and cognitive inhibitory functions in a relatively large group of children and adolescents with ADHD who had never previously been exposed to medication. METHOD: Nineteen boys with ADHD and 27 healthy age- and IQ-matched boys underwent functional MRI to compare brain activation during performance of tasks that assessed motor response inhibition (go/no go task), cognitive interference inhibition (motor Stroop task), and cognitive flexibility (switch task). RESULTS: Boys with ADHD showed decreased activation in the left rostral mesial frontal cortex during the go/no go task and decreased activation in the bilateral prefrontal and temporal lobes and right parietal lobe during the switch task. No significant group differences were observed during motor Stroop task performance. CONCLUSION: Abnormal brain activation was observed in medication-naive children and adolescents with ADHD during tasks involving motor inhibition and task switching, suggesting that hypoactivation in this patient group is unrelated to long-term stimulant exposure. Furthermore, functional abnormalities are task-specific and extend from frontostriatal to parietal and temporal cortices.

Abnormal brain activation during inhibition and error detection in medication-naive adolescents with ADHD.

OBJECTIVE: Patients with attention deficit hyperactivity disorder (ADHD) and a medication history have shown abnormal brain activation in prefrontal and striatal brain regions during cognitive challenge. Previous findings have been confounded, however, by potential long-term effects of stimulant medication exposure and group discrepancies in task performance. The aim of this study was to investigate whether medication-naive adolescents with ADHD would still show abnormal brain activation in prefrontal brain regions during motor response inhibition in a task designed to control for intergroup performance discrepancies. METHOD: Rapid, event-related functional magnetic resonance imaging was used to compare brain activation in 16 medication-naive ADHD adolescents and 21 IQ-, age-, and sex-matched healthy comparison volunteers during a challenging, idiosyncratically adjusted task that required withholding of a triggered motor response. The design, which manipulated task parameters to force each subject to fail on 50% of trials, ensured that subjects worked at the edge of their own inhibitory performance, thereby controlling for intersubject and intergroup performance discrepancies and furthermore allowing for investigation of differences in brain activation related to inhibition and inhibition failure. RESULTS: Medication-naive adolescents with ADHD showed significantly reduced brain activation in the right inferior prefrontal cortex during successful motor response inhibition and in the precuneus and posterior cingulate gyrus during inhibition failure, both of which correlated with behavioral scores of ADHD. CONCLUSIONS: The study shows that abnormal brain activation during inhibitory challenge in ADHD is specific to the disorder, since it persists when medication history and performance discrepancies are excluded.

Cognitive abnormalities in schizophrenia and schizophrenia-like psychosis of epilepsy.

Twenty-six patients with schizophrenia and 12 patients with schizophrenia-like psychosis of epilepsy (SLPE) were compared to 38 healthy volunteers and 12 nonpsychotic patients with epilepsy to determine the contribution of psychosis to the pattern of cognition. Tests of memory and executive function were used. The schizophrenic group was more cognitively impaired than the SLPE and comparison groups. The profile of neuropsychological impairment in SLPE resembled that of schizophrenia and is unlikely to be explained solely by temporal lobe dysfunction. These results do not support the concept of SLPE as an independent nosological entity.

Nonepileptic seizures following general anesthetics: a report of five cases.

Five patients who developed seizures following a general anesthetic are described. It is not possible to determine retrospectively whether or not the initial attacks were definitely epileptic, but these patients all subsequently received a diagnosis of psychological nonepileptic convulsions/seizures (also known as pseudoseizures, psychogenic nonepileptic seizures, and nonepileptic attack disorder) established by video/EEG telemetry or ictal EEG recordings. In two cases there was evidence of concurrent epilepsy. We suggest that nonepileptic seizures may develop following postanesthetic seizures and that a psychogenic basis for seizures occurring after general anesthetics needs to be considered.

An evaluation of cognitive behavioral therapy as a treatment for dissociative seizures: a pilot study.

OBJECTIVE: To evaluate in an open trial the effectiveness of cognitive behavioral therapy as a treatment of adults with dissociative seizures (i.e., "pseudoseizures"). BACKGROUND: Although suggestions have been made concerning the management of patients with dissociative seizures, no studies have previously evaluated the systematic use of cognitive behavioral therapy in the treatment of this disorder. METHOD: Twenty patients diagnosed with dissociative seizures were offered treatment comprising 12 sessions of cognitive behavioral therapy. Principal outcome measures were dissociative seizure frequency and psychosocial functioning, including improvement in employment status and mood. Measures were administered before treatment, at the end of treatment, and at a 6-month follow-up. RESULTS: Treatment was completed by 16 patients (questionnaire measures were not available for 4 patients who discontinued treatment). Following treatment, there was a highly significant reduction in seizure frequency and an improvement in self-rated psychosocial functioning. These improvements were maintained at the 6-month follow-up. There was also a tendency for patients to have improved their employment status between the start of treatment and the 6-month follow-up period. CONCLUSIONS: In this open prospective trial, cognitive behavioral therapy was associated with a reduction in dissociative seizure frequency and an improvement in psychosocial functioning in adults with dissociative seizures.

Frontal lobe N-acetylaspartate correlates with psychopathology in schizophrenia: a proton magnetic resonance spectroscopy study.

INTRODUCTION: Clinical, neuropsychological and functional neuroimaging studies in schizophrenia suggest impaired frontal lobe function, especially of the dorsolateral prefrontal region (DLPFR). This dysfunction has in particular been associated with negative or "deficit" symptoms. Despite these findings, morphological studies have failed to show consistent structural abnormalities in the frontal lobe. This may be because existing techniques are not sensitive enough to detect structural abnormalities or that dysfunction in the frontal lobe is caused by lesions elsewhere. We used volume-localised proton magnetic resonance spectroscopy (1H-MRS) to measure N-acetylaspartate (NAA), a neuronal marker, to evaluate the neuronal integrity of the dorsolateral prefrontal region in schizophrenic patients with persistent negative symptoms and in healthy comparison subjects. METHOD: Twenty-five patients who fulfilled DSM-IV criteria for schizophrenia and met the criteria for the Deficit syndrome were compared to 26 healthy controls matched for age and gender. Bilateral proton MR spectra were collected from a 2-cm(3) volume in the dorsolateral prefrontal region and the absolute concentrations of N-acetylaspartate, choline (Cho) and creatine+phosphocreatine (Cr+PCr) were measured. RESULTS: There was a significant negative correlation between severity of symptoms and NAA concentration in the schizophrenic patients. This was more marked for positive symptoms and for general psychopathology than for negative symptoms. There was also a significant correlation between NAA concentration and social functioning within the schizophrenic group. There were no significant differences between the two groups for the three metabolites. CONCLUSIONS: The negative association between severity of symptoms and NAA in schizophrenic patients and an association of NAA with social functioning suggest that NAA may be an indicator of disease severity. The lack of significant mean difference in NAA between the two groups suggests that there is no marked neuronal loss in the dorsolateral prefrontal region in schizophrenia.

Quantitative magnetic resonance imaging of the amygdala in temporal lobe epilepsy-clinico-pathological correlations (a pilot study).

PURPOSE: We carried out a pilot study of quantitative volumetric MRI of the amygdala in patients undergoing surgery for intractable temporal lobe epilepsy. We wished to explore whether amygdala volume correlated with pre-operative clinical variables and post-operative outcome. METHODS: Ten patients had detailed volumetric measurements of their amygdala and hippocampus according to operationalised anatomical criteria from an optimised MRI imaging sequence. A ratio of volumes from the unoperated to operated side was calculated. Surgical specimens were examined histologically for astrocytosis. RESULTS: The volumes of the amygdala and hippocampus on the operated side were significantly smaller than on the unoperated side. More severe astrocytosis appeared to go along with smaller volume ratios but the relationship was not significant. There were few significant correlations between volumes measures and clinical or outcome variables. CONCLUSION: Reductions in amygdala volume in the to-be-operated temporal lobe in patients with medically intractable epilepsy can be reliably detected using volumetric MRI. Accurate amygdala volume measures do not appear to exert a significant effect on clinical presentation and outcome in the presence of hippocampal volumes reductions, but may be useful in confirming bilateral pathology. Larger studies examining clinico-pathological correlations are recommended.

Psychosis with good prognosis in Afro-Caribbean people now living in the United Kingdom

OBJECTIVES - to compare the course and outcome of psychotic illness in a group of Afro-Caribbean patients resident in the United Kingdom and a group of white British patients. DESIGN - cohort study of consecutive admissions followed up for four years. SUBJECTS - 113 patients with psychotic illness of recent onset admitted to two south London hospitals. MAIN OUTCOME MEASURES - course of illness, history of self harm, social disability, treatment received, and hospital use adjusted for socioeconomic origin. RESULTS - the Afro-Caribbean group spent more time in a recovered state during the follow up period (adjusted odds ratio 5.0; 95 percent confidence interval 1.7 10 14.5), were less likely to have had a continuous illness (0.3; 0.1 to 0.8), were less at risk of self harm (0.2; 0.1 to 0.8), and were less likely to have been prescribed antidepressant treatment (0.3; 0.1 to 0.9). There were no differences in hospital use, but the Afro-Caribbean group had more involuntary admissions (8.9; 2.1 to 35.6) and more imprisonments over the follow up period (9.2; 1.6 to 52.3). CONCLUSIONS - Afro-Caribbean patients in the United Kingdom have a better outcome after psychiatric illness than do white people. The combination of high incidence and more benign course of illness of psychotic illness in this group may be due, at least in part, to a greater exposure to precipitants in the social environment. (AU)

The functional psychoses in Afro-Caribbean

When 54 Afro-Caribbean and 49 white British consecutive psychotic in-patients were prospectively studied for clinical differences in course of illness and pattern of symptoms, no major differences were found. This does not support the hypothesis that misdiagnosis within the psychoses can explain the higher admission rates of schizophrenia calculated for Afro-Caribbean population. (AU)