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Biomedical subjects

Alan H Lockwood

Publications and source records attributed to Alan H Lockwood.

At least 19 recordsLinked to original sources
PubMed2005

Cognitive therapy for irritable bowel syndrome is associated with reduced limbic activity, GI symptoms, and anxiety.

This study sought to identify brain regions that underlie symptom changes in severely affected IBS patients undergoing cognitive therapy (CT). Five healthy controls and 6 Rome II diagnosed IBS patients underwent psychological testing followed by rectal balloon distention while brain neural activity was measured with O-15 water positron emission tomography (PET) before and after a brief regimen of CT. Pre-treatment resting state scans, without distention, were compared to post-treatment scans using statistical parametric mapping (SPM). Neural activity in the parahippocampal gyrus and inferior portion of the right cortex cingulate were reduced in the post-treatment scan, compared to pre-treatment (x, y, z coordinates in MNI standard space were -30, -12, -30, P=0.017; 6, 34, -8, P=0.023, respectively). Blood flow values at these two sites in the controls were intermediate between those in the pre- and post-treatment IBS patients. Limbic activity changes were accompanied by significant improvements in GI symptoms (e.g., pain, bowel dysfunction) and psychological functioning (e.g., anxiety, worry). The left pons (-2, -26, -28, P=0.04) showed decreased neural activity which was correlated with post-treatment anxiety scores. Changes in neural activity of cortical-limbic regions that subserve hypervigilance and emotion regulation may represent biologically oriented change mechanisms that mediate symptom improvement of CT for IBS.

Adult↗
PubMed2005

Mapping the 40-Hz auditory steady-state response using current density reconstructions.

We mapped the 40-Hz aSSR from nine normal subjects using PET-independent low-resolution electroencephalographic tomography (LORETA) as well as PET-weighted LORETA and minimum norm (MinNorm) current density reconstructions. In grand mean data, PET-independent LORETA identified seven sites with peaks in current density in right temporal lobe, right brainstem/cerebellum, right parietal lobe, left cerebellum/temporal lobe, and right frontal lobe. PET-weighted LORETA found six of the same sites as the PET-independent LORETA: the right brainstem source was eliminated and two right-frontal sources were added. Both LORETA analyses revealed considerable phase dispersion across identified sources. In both LORETA analyses, the relative time course of activation measured from an arbitrary starting phase progressed from right temporal lobe to right mid-frontal lobe to right parietal-frontal to right inferior parietal and finally to left cerebellum and left temporal lobe. MinNorm analysis incorporating PET information identified sources in the same locations as specified in the PET data. These sources were synchronized, with their amplitudes peaking almost simultaneously. Both PET-independent and PET-weighted LORETA results suggest that the aSSR is: (1) the result of a reverberating network with two or more groups of sources that recurrently excite each other or (2) the result of sequential auditory processing through various levels of a hierarchical network. In contrast, the PET-weighted MinNorm results suggest that the 40-Hz response represents simultaneous activation over widely spaced areas of the brain, perhaps due to synchronization of gamma-band activity to a common neural clock.

Acoustic Stimulation↗
PubMed2005

Tinnitus.

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Humans↗
PubMed2005

Neurodegenerative diseases: an overview of environmental risk factors.

The population of the United States is aging, and an ever-increasing number of Americans are afflicted with neurodegenerative diseases. Because the pathogenesis of many of these diseases remains unknown, we must consider that environmental factors may play a causal role. This review provides an overview of the epidemiologic evidence for environmental etiologies for neurodegenerative diseases such as Alzheimer disease, Parkinson disease, parkinsonian syndromes (multiple system atrophy and progressive supranuclear palsy), and amyotrophic lateral sclerosis. Epidemiologic evidence for an association between environmental agents' exposure and neurodegenerative diseases is not conclusive. However, there are indications that there may be causal links, and the need for more research is obvious.

Age Factors↗
PubMed2004

Functional imaging during covert auditory attention in multiple sclerosis.

Recent literature suggests that the brain in multiple sclerosis (MS) undergoes reorganization that subserves the performance of visual and motor tasks. We identified sites of cerebral activity in 16 MS patients while performing a covert attention (CA) task, presented in the auditory modality. Positron emission tomography (PET) revealed activation of rostral/dorsal anterior cingulate cortex (ACC) in normal subjects studied previously. Activity in this region was not significant in MS patients, but there was a large region of activity in superior temporal cortex. Decreased activation of frontal attentional networks and greater activity in sensory/perceptual cortical areas (auditory association cortex) suggests a reduction of transmission along white matter tracts connecting these regions. This study demonstrates cingulate hypoactivity and cerebral reorganization during auditory attention in MS.

Acoustic Stimulation↗
PubMed2004

PET imaging of the 40 Hz auditory steady state response.

The auditory steady state response (aSSR) is an oscillatory electrical potential recorded from the scalp induced by amplitude-modulated (AM) or click/tone burst stimuli. Its clinical utility has been limited by uncertainty regarding the specific areas of the brain involved in its generation. To identify the generators of the aSSR, 15O-water PET imaging was used to locate the regions of the brain activated by a steady 1 kHz pure tone, the same tone amplitude modulated (AM) at 40 Hz and the specific regions of the brain responsive to the AM component of the stimulus relative to the continuous tone. The continuous tone produced four clusters of activation. The boundaries of these activated clusters extended to include regions in left primary auditory cortex, right non-primary auditory cortex, left thalamus, and left cingulate. The AM tone produced three clusters of activation. The boundaries of these activated clusters extended to include primary auditory cortex bilaterally, left medial geniculate and right middle frontal gyrus. Two regions were specifically responsive to the AM component of the stimulus. These activated clusters extended to include the right anterior cingulate near frontal cortex and right auditory cortex. We conclude that cortical sites, including areas outside primary auditory cortex, are involved in generating the aSSR. There was an unexpected difference between morning and afternoon session scans that may reflect a pre- versus post-prandial state. These results support the hypothesis that a distributed resonating circuit mediates the generation of the aSSR.

Adult↗
PubMed2004

Mapping the neural systems that mediate the Paced Auditory Serial Addition Task (PASAT).

The paced auditory serial addition task (PASAT), in which subjects hear a number-string and add the two most-recently heard numbers, is a neuropsychological test sensitive to cerebral dysfunction. We mapped the brain regions activated by the PASAT using positron emission tomography (PET) and 15O-water to measure cerebral blood flow. We parsed the PASAT by mapping sites activated by immediate repetition of numbers and by repetition of the prior number after the presentation of the next number in the series. The PASAT activated dispersed non-contiguous foci in the superior temporal gyri, bifrontal and biparietal sites, the anterior cingulate and bilateral cerebellar sites. These sites are consistent with the elements of the task that include auditory perception and processing, speech production, working memory, and attention. Sites mediating addition were not identified. The extent of the sites activated during the performance of the PASAT accounts for the sensitivity of this test and justifies its use in a variety of seemingly disparate conditions.

Acoustic Stimulation↗
PubMed2004

Blood ammonia levels and hepatic encephalopathy.

The importance of measurements of the blood ammonia concentration in the evaluation of patients with known or suspected hepatic encephalopathy (HE) is still disputed in spite of a general acknowledgment that ammonia is important in the pathogenesis of the disorder. Several recent studies have suggested that it is not necessary to utilize arterial blood when measuring ammonia in the blood. Venous blood or a computation of the partial pressure of ammonia gas in blood samples may suffice. The value of blood ammonia measurements is limited by the fact that this is not the variable that is the most important. Ideally, one would like to know how much ammonia enters the brain, not how much is in the blood. The blood-brain barrier (BBB) is the critical and poorly understood element in this relationship. Although both ammonia in the gas and ionic forms cross the BBB, the ease with which this movement occurs is significantly higher in patients with HE. In the absence of simple methods to measure the brain ammonia metabolic rate and to assess the BBB to ammonia in conjunction with measuring the blood ammonia concentration, the variables that would be the most desirable to measure, the use of arterial and/or venous blood measurements needs to be coupled with a complete understanding of the physiology of cerebral ammonia metabolism.

Ammonia↗
PubMed2004

Human testing of pesticides: ethical and scientific considerations.

I reviewed ethical and scientific aspects of 6 human pesticide-dosing studies submitted to the Environmental Protection Agency (EPA) for consideration during the pesticide reregistration process. All had serious ethical or scientific deficiencies-or both-including unacceptable informed consent procedures, unmanaged financial conflicts of interest, inadequate statistical power, inappropriate test methods and endpoints, and distorted results. Given today's knowledge of the effects of pesticides, there is no assurance that any such study can be completely free of short-term risks, long-term risks, or both. Therefore, there is no basis for allowing pesticide studies to continue or for using them during the pesticide reregistration process. An EPA committee that is free from political and financial conflicts of interest should review this practice.

Analysis of Variance↗
PubMed2002

Tinnitus.

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Algorithms↗
PubMed2002

Brain imaging of the effects of lidocaine on tinnitus.

Using a single-blind placebo-controlled design, we mapped lidocaine related changes in neural activity, measured by regional cerebral blood flow (rCBF) with (15)O-H(2)O positron emission tomography. Intravenous lidocaine produced both increases and decreases in the loudness of tinnitus. The change in tinnitus loudness was associated with a statistically significant change in neural activity in the right temporal lobe in auditory association cortex. Decreases in tinnitus loudness resulted in larger changes in rCBF than increases. The unilateral activation pattern associated with tinnitus, in contrast with the bilateral activation produced by a real sound, suggests that tinnitus originates in the central auditory system rather than the cochlea. In addition, generalized lidocaine effects were found in the basal ganglia, thalamus, and a region spanning the Rolandic fissure.

Acoustic Stimulation↗
PubMed2002

Hepatic encephalopathy.

Many patients with cirrhosis of the liver who appear to be overtly normal, using standard bedside examination techniques, test in the impaired range on one or more neuropsychological tests. These impairments affect the quality of life. Improvement in affected cognitive domains and the quality of life may follow the institution of treatment.

Brain↗
PubMed2002

Correlations between cerebral glucose metabolism and neuropsychological test performance in nonalcoholic cirrhotics.

Many cirrhotics have abnormal neuropsychological test scores. To define the anatomical-physiological basis for encephalopathy in nonalcoholic cirrhotics, we performed resting-state fluorodeoxyglucose positron emission tomographic scans and administered a neuropsychological test battery to 18 patients and 10 controls. Statistical parametric mapping correlated changes in regional glucose metabolism with performance on the individual tests and a composite battery score. In patients without overt encephalopathy, poor performance correlated with reductions in metabolism in the anterior cingulate. In all patients, poor performance on the battery was positively correlated (p < 0.001) with glucose metabolism in bifrontal and biparietal regions of the cerebral cortex and negatively correlated with metabolism in hippocampal, lingual, and fusiform gyri and the posterior putamen. Similar patterns of abnormal metabolism were found when comparing the patients to 10 controls. Metabolic abnormalities in the anterior attention system and association cortices mediating executive and integrative function form the pathophysiological basis for mild hepatic encephalopathy.

Aged↗
PubMed2002

Positron emission tomography in the study of hepatic encephalopathy.

Positron emission tomography (PET) is a powerful and versatile tool for the investigation of hepatic encephalopathy (HE). This nuclear medicine imaging technique produces quantitative images of the distribution of a radiopharmaceutical at one or more times after its administration. Thus, PET images can be used as data in mathematical models of physiologically important processes, including cerebral blood flow, an index of neural activity, or glucose and ammonia metabolism. Using PET, we have demonstrated abnormalities in all of these processes in patients, even though many had only minimal HE. In HE patients we have found increases in the cerebral ammonia metabolic rate, because of hyperammonemia and an increase in the permeability of the blood-brain barrier to ammonia and abnormal patterns of blood flow and glucose metabolism. In a recent collaborative study, alterations in the resting glucose metabolic rate were found to have significant correlations with a variety of neuropsychological tests used to detect mild HE including Trailmaking A and B, symbol-digit, and other tests. Activation techniques have not yet been applied to map sites affected by HE, but recent data using the paced serial auditory addition test and an auditory continuous performance task have proven to be sensitive indicators in minimally impaired patients. The full potential of PET to evaluate neurotransmitter function is as yet unrealized.

Ammonia↗