The neurological system (entire body) operates via electric and electromagnetic signals. Does it not make sense to address neurological disease states such as Alzheimer's from an electrophysiological or electrochemical rather than from a chemical based point of view? Researchers continue to declare 'YEARS' before meaningful rTMS treatment for Alzheimer's sufferers when the researchers below have already proved at least some therapeutic intervention.
50 years of pulsed electromagnetic field therapy research suggests that some sort type of electrophysiological deficit exists in neurological disease states and that it should be addressed via same electrophysiological channel.
The addressable conditions for which there is peer reviewed research; include (but are not limited to) epilepsy, Parkinson's, migraine, cluster and other headache syndromes, severe PMS, attention deficit disorder ADD, attention deficit hyperactivity disorder ADHD, depression, schizophrenia, anxiety, insomnia and sleeping disorders in general, muscle twitch, tremor disorders, muscle weakness, chronic wounds, bone non-unions and endometriosis.Several hundred pulsed electromagnetic field therapy citations contained in our research bibliographies below are linked directly to PubMed a service of the U.S. National Library of Medicine and the U.S. National Institutes of Health.
1: Ann Neural. 2003 Jun;53(6):824; author reply 824-5. Related Articles, Links
Comment on:
* Ann Neurol. 2003 Jan;53(1):102-8.
Motor cortex hyperexcitability to
transcranial magnetic stimulation in Alzheimer's disease:
evidence of impaired glutamatergic neurotransmission?
Di Lazzaro V, Oliviero A, Pilato F, Saturno E, Dileone M, Tonali
PA.
Publication Types:
* Comment
* Letter
PMID: 12783435 [PubMed - indexed for MEDLINE]
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2: Neuropsychologia. 2003;41(8):952-67. Related Articles, Links
Spelling via semantics and phonology:
exploring the effects of age, Alzheimer's disease, and primary
semantic impairment.
Cortese MJ, Balota DA, Sergent-Marshall SD, Buckner RL.
Department of Psychology, Morehead State University, 601 Ginger
Hall, Morehead, KY 40351, USA.
Spelling performance across a common set of stimuli was examined
in young adults, healthy older adults, individuals with early
stage dementia of the Alzheimer's type (DAT), and four
individuals with a primary semantic impairment (PSI). The
stimuli included homophones and low-frequency sound-to-spelling
consistent (i.e. words with more predictable spellings) and
inconsistent words (i.e. words with less predictable spellings).
The results indicate that when spelling homophonic words
(spelling/pleIn/ as plane versus plain), younger adults and to a
greater extent individuals with PSI placed relatively more
emphasis on phonological information (i.e. spell the word based
on sound-to-spelling principles) whereas healthy older adults
and individuals with DAT placed relatively more emphasis on
semantic information (i.e. spell the word based on the dominant
usage). For non-homophonic words, large consistency effects
(spelling plaid as plad) were observed for both individuals with
DAT and individuals with PSI. It is proposed that the decrease
in accuracy for inconsistent words has different bases in DAT
and PSI. We propose that deficits in attentional control (i.e.
selection) underlie performance in DAT whereas disruption of
semantic representations underlies performance in PSI.
PMID: 12667531 [PubMed - indexed for MEDLINE]
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3: Hippocampus. 2003;13(1):67-80. Related Articles, Links
Encoding of novel picture pairs activates
the perirhinal cortex: an fMRI study.
Pihlajamaki M, Tanila H, Hanninen T, Kononen M, Mikkonen M,
Jalkanen V, Partanen K, Aronen HJ, Soininen H.
Department of Neuroscience and Neurology, University of Kuopio,
Kuopio, Finland.
It is well established in nonhuman primates that the medial
temporal lobe (MTL) structures, the hippocampus and the
entorhinal and perirhinal cortices, are necessary for
declarative memory encoding. In humans, the neuropathological
and neuropsychological changes in early Alzheimer's disease (AD)
further support a role for the rhinal cortex in the
consolidation of new events into long-term memory. Little is
known, however, regarding the function of the rhinal cortex in
humans in vivo. To examine the participation of the
interconnected MTL structures as well as the whole-brain network
of activated brain areas in visual associative long-term memory,
functional magnetic resonance imaging (fMRI) was used to
determine the brain regions that are activated during encoding
and retrieval of paired pictures in 12 young control subjects.
The most striking finding in the MTL activation pattern was the
consistent activation of the perirhinal cortex in the
encoding-baseline and encoding-retrieval comparisons with a
strict statistical threshold (P < 0.00001). In contrast, no
perirhinal cortex activation was detected in the
retrieval-baseline or retrieval-encoding comparisons even with a
low statistical threshold (P < 0.05). The location of the
perirhinal activation area was in the transentorhinal part of
the perirhinal cortex, in the medial bank of the collateral
sulcus. The hippocampus and the more posterior parahippocampal
gyrus were activated in both encoding and retrieval conditions.
During the encoding processing, MTL activations were more
consistent and the hippocampal activation area located more
anteriorly than during retrieval. The frontal, parietal,
temporal, and occipital association cortices were also activated
in the encoding-baseline and retrieval-baseline comparisons. The
data suggest that encoding, but not retrieval, of novel picture
pairs activates the perirhinal cortex. To our knowledge, this is
the first fMRI study reporting encoding activation in this
transentorhinal part of the perirhinal cortex, the site of the
very earliest neuropathological changes in AD.
PMID: 12625459 [PubMed - indexed for MEDLINE]
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4: Methods Find Exp Clin Pharmacol. 2002;24 Suppl D:17-20. Related Articles, Links
Simultaneous ERP and event-related fMRI:
focus on the time course of brain activity in target detection.
Mulert C, Jager L, Pogarell O, Bussfeld P, Schmitt R, Juckel G,
Hegerl U.
Laboratory for Clinical Neurophysiology, Department of
Psychiatry, LMU, Munich, Germany.
The event-related P300 potential has been widely used in
neurophysiological research. It is usually evoked with an
oddball paradigm. One main reason for its broad application in
neurophysiological research is the fact that in several
brain/mental diseases, such as Alzheimer's disease or
schizophrenia, attenuations of the P300 amplitude and latency
have been described. However, a precise correlation of the scalp
data to the underlying brain regions was not possible, as the
correct localization of the generators of scalp-measured
electroencephalogram (EEG) data was limited, due to the low
spatial resolution of EEG-data. With the availability of modern
imaging technologies, functional Magnetic Resonance Imaging
(fMRI) in particular, the underlying brain activations could be
detected using an oddball task. Although the spatial resolution
of fMRI is excellent, the time resolution is restricted. For a
comprehensive understanding of the brain activity underlying the
P300 paradigm, we have used a combination of EEG and fMRI to get
a precise localization and a high-time resolution of the
underlying brain activity.
PMID: 12575464 [PubMed - indexed for MEDLINE]
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5: Ann Neurol. 2003 Jan;53(1):102-8. Related Articles, Links
Motor cortex excitability in Alzheimer's
disease: A transcranial magnetic stimulation study.
Ferreri F, Pauri F, Pasqualetti P, Fini R, Dal Forno G, Rossini
PM.
Department of Neurology, University Campus Biomedico.
Motor deficits affect patients with Alzheimer's disease only at
later stages. Recent studies demonstrate that the primary motor
cortex is affected by neuronal degeneration accompanied by the
formation of amyloid plaques and neurofibrillary tangles. It is
conceivable that neuronal loss is compensated by reorganization
of the neural circuitries occurring along the natural course of
the disease, thereby maintaining motor performances in daily
living. Cortical motor output to upper limbs was tested via
motor-evoked potentials from forearm and hand muscles elicited
by transcranial magnetic stimulation of motor cortex in 16
patients with mild Alzheimer's disease without motor deficits.
Motor cortex excitability was increased, and the center of
gravity of motor cortical output, as represented by excitable
scalp sites, showed a frontal and medial shift, without
correlated changes in the site of maximal excitability
(hot-spot). This may indicate functional reorganization,
possibly after the neuronal loss in motor areas.
Hyperexcitability might be caused by a dysregulation of the
intracortical GABAergic inhibitory circuitries and selective
alteration of glutamatergic neurotransmission. Such findings
suggest that motor cortex hyperexcitability and reorganization
allows prolonged preservation of motor function during the
clinical course of Alzheimer's disease.
PMID: 12509853 [PubMed - in process]
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6: Brain Res Cogn Brain Res. 2002 Nov;14(3):347-56. Related Articles, Links
Functional magnetic resonance imaging of
brain activity in the visual oddball task.
Ardekani BA, Choi SJ, Hossein-Zadeh GA, Porjesz B, Tanabe JL,
Lim KO, Bilder R, Helpern JA, Begleiter H.
Center for Advanced Brain Imaging, Nathan Kline Institute for
Psychiatric Research, 140 Old Orangeburg Road, Orangeburg, NY
10962, USA.
Abnormalities in the P300 ERP, elicited by the oddball task and
measured using EEG, have been found in a number of central
nervous system disorders including schizophrenia, Alzheimer's
disease, and alcohol dependence. While electrophysiological
studies provide high temporal resolution, localizing the P300
deficit has been particularly difficult because the measurements
are collected from the scalp. Knowing which brain regions are
involved in this process would elucidate the behavioral
correlates of P300. The aim of this study was to determine the
brain regions involved in a visual oddball task using fMRI. In
this study, functional and high-resolution anatomical MR images
were collected from seven normal volunteers. The data were
analyzed using a randomization-based statistical method that
accounts for multiple comparisons, requires no assumptions about
the noise structure of the data, and does not require spatial or
temporal smoothing. Activations were detected (P<0.01)
bilaterally in the supramarginal gyrus (SMG; BA 40), superior
parietal lobule (BA 7), the posterior cingulate gyrus, thalamus,
inferior occipitotemporal cortex (BA 19/37), insula,
dorsolateral prefrontal cortex (BA 9), anterior cingulate cortex
(ACC), medial frontal gyrus (BA 6), premotor area, and cuneus
(BA 17). Our results are consistent with previous studies that
have observed activation in ACC and SMG. Activation of thalamus,
insula, and the occipitotemporal cortex has been reported less
consistently. The present study lends further support to the
involvement of these structures in visual target detection.
PMID: 12421658 [PubMed - indexed for MEDLINE]
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7: Neuroimage. 2002 Nov;17(3):1403-14. Related Articles, Links
Functional imaging of visuospatial
processing in Alzheimer's disease.
Prvulovic D, Hubl D, Sack AT, Melillo L, Maurer K, Frolich L,
Lanfermann H, Zanella FE, Goebel R, Linden DE, Dierks T.
Department of Psychiatry, University of Frankfurt, Frankfurt,
Germany.
Alzheimer's disease (AD) is known to cause a variety of
disturbances of higher visual functions that are closely related
to the neuropathological changes. Visual association areas are
more affected than primary visual cortex. Additionally, there is
evidence from neuropsychological and imaging studies during rest
or passive visual stimulation that the occipitotemporal pathway
is less affected than the parietal pathway. Our goal was to
investigate functional activation patterns during active
visuospatial processing in AD patients and the impact of local
cerebral atrophy on the strength of functional activation.
Fourteen AD patients and fourteen age-matched controls were
measured with functional magnetic resonance imaging (fMRI) while
they performed an angle discrimination task. Both groups
revealed overlapping networks engaged in angle discrimination
including the superior parietal lobule (SPL), frontal and
occipitotemporal (OTC) cortical regions, primary visual cortex,
basal ganglia, and thalamus. The most pronounced differences
between the two groups were found in the SPL (more activity in
controls) and OTC (more activity in patients). The differences
in functional activation between the AD patients and controls
were partly explained by the differences in individual SPL
atrophy. These results indicate that parietal dysfunction in
mild to moderate AD is compensated by recruitment of the ventral
visual pathway. We furthermore suggest that local cerebral
atrophy should be considered as a covariate in functional
imaging studies of neurodegenerative disorders.
PMID: 12414280 [PubMed - indexed for MEDLINE]
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8: Hum Brain Mapp. 2002 Dec;17(4):230-6. Related Articles, Links
Novelty detection and repetition
suppression in a passive picture viewing task: a possible
approach for the evaluation of neuropsychiatric disorders.
Jessen F, Manka C, Scheef L, Granath DO, Schild HH, Heun R.
Department of Psychiatry, University of Bonn, Bonn, Germany.
The applicability of functional magnetic resonance imaging
(fMRI) in patients with Alzheimer's disease (AD) or
schizophrenia is frequently limited by cognitive impairment,
which prevents the adequate execution of complex tasks. An
experimental design that puts only minor demands on the
patients' cognitive ability but engages disease-relevant brain
structures would be of benefit. Novelty detection and repetition
suppression are two basic components of memory that might be
used to investigate specific brain areas under these conditions.
Novelty detection has been related to hippocampal activation
increases. Stimulus repetition related activation decreases
(suppression) have been observed in the extrastriate cortex and
have been related to perceptual priming. Both processes have
been examined primarily in neuroimaging studies with complex
cognitive tasks. We used event-related fMRI to investigate
novelty- and repetition-related effects in an attended but
passive picture-viewing task in healthy subjects. The
differential activation, detected in the novel vs. repeated
contrast, was located in the bilateral anterior hippocampus and
in bilateral occipital and inferior-temporal areas. The
hippocampal activation is of interest because medial temporal
lobe lesions are key features in AD and schizophrenia. The
repetition-related activation decreases in the extrastriate
areas are of potential value in investigating the conflicting
results regarding perceptual priming impairment in both
disorders. Our results indicate that activation of
disease-relevant brain regions under passive task conditions is
possible. This might increase the utility of functional imaging
in cognitively impaired patients. Copyright 2002 Wiley-Liss,
Inc.
PMID: 12395390 [PubMed - indexed for MEDLINE]
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9: Neurosci Lett. 2002 Sep 6;329(3):293-6. Related Articles, Links
Motor cortex excitability in Alzheimer
disease: one year follow-up study.
Pennisi G, Alagona G, Ferri R, Greco S, Santonocito D,
Pappalardo A, Bella R.
Department of Neurological Sciences, University of Catania,
Azienda Policlinico dell' Universita, Via S. Sofia, 78, 95123
Catania, Italy.
Seventeen patients affected by Alzheimer disease (AD) underwent
two transcranial magnetic stimulation (TMS) studies separated by
an interval of 12 months, in order to monitor possible changes
in motor cortex excitability. After the first examination, all
patients were treated with cholinesterase inhibitor drugs. Motor
threshold (MT), amplitude of motor evoked potentials and central
motor conduction time were considered. After one year, the mean
MT values showed a decrease significantly correlated with the
severity of cognitive involvement, evaluated by means of the
Mini Mental State Examination (MMSE). The difference in MT
between the two recording sessions showed no significant
correlation with the difference in MMSE score. One year of
treatment with cholinesterase inhibitor drugs did not stop the
progressive increase in motor cortex excitability. Serial
analysis of TMS might represent a method to monitor the rate of
change in motor cortex excitability in patients with AD.
PMID: 12183034 [PubMed - indexed for MEDLINE]
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10: Neurology. 2002 Aug 13;59(3):392-7. Related Articles, Links
Noninvasive in vivo assessment of
cholinergic cortical circuits in AD using transcranial magnetic
stimulation.
Di Lazzaro V, Oliviero A, Tonali PA, Marra C, Daniele A, Profice
P, Saturno E, Pilato F, Masullo C, Rothwell JC.
Institute of Neurology, Catholic University, Largo A. Gemelli 8,
00168 Rome, Italy.
BACKGROUND: A recently devised test of motor cortex excitability
(short latency afferent inhibition) was shown to be sensitive to
the blockade of muscarinic acetylcholine receptors in healthy
subjects. The authors used this test to assess cholinergic
transmission in the motor cortex of patients with AD. METHODS:
The authors evaluated short latency afferent inhibition in 15
patients with AD and compared the data with those of 12
age-matched healthy controls. RESULTS: Afferent inhibition was
reduced in the patients (mean responses +/- SD reduced to 85.7%
+/- 15.8% of the test size) compared with controls (mean
responses +/- SD reduced to 45.3% +/- 16.2% of the test size; p
< 0.001, unpaired t-test). Administration of a single oral
dose of rivastigmine improved afferent inhibition in a subgroup
of six patients. CONCLUSIONS: The findings suggest that this
method can be used as a noninvasive test of cholinergic pathways
in AD. Future studies are required to evaluate whether short
latency afferent inhibition measurements have any consistent
clinical correlates.
PMID: 12177373 [PubMed - indexed for MEDLINE]
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11: J Neurosci. 2002 Aug 15;22(16):7218-24. Related Articles, Links
Compromised hemodynamic response in amyloid
precursor protein transgenic mice.
Mueggler T, Sturchler-Pierrat C, Baumann D, Rausch M,
Staufenbiel M, Rudin M.
Central Technologies, Novartis Pharma, AG, CH-4002 Basel,
Switzerland.
APP23 transgenic mice overexpressing amyloid precursor protein
(APP751) reproduce neuropathological changes associated with
Alzheimer's disease such as high levels of amyloid plaques,
cerebral amyloid angiopathy, and associated vascular
pathologies. Functional magnetic resonance imaging (fMRI) was
applied to characterize brain functionality in these mice
through global pharmacological stimulation. The cerebral
hemodynamic response to infusion of the GABA(A) antagonist
bicuculline was significantly reduced in aged APP23 mice
compared with age-matched wild-type littermates. This is in part
attributable to a compromised cerebrovascular reactivity, as
revealed by the reduced responsiveness to vasodilatory
stimulation by acetazolamide. The study shows that fMRI is a
sensitive tool to phenotype genetically engineered animals
modeling neuropathologies.
PMID: 12177216 [PubMed - indexed for MEDLINE]
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12: Ann Neurol. 2002 Apr;51(4):491-8. Related Articles, Links
Subjective memory complaints: objective
neural markers in patients with Alzheimer's disease and major
depressive disorder.
Gron G, Bittner D, Schmitz B, Wunderlich AP, Riepe MW.
Memory Clinic, University of Ulm, Germany.
Patients with probable Alzheimer's disease and depressive
patients frequently present with subjective memory complaints.
Objective distinction of underlying neuronal substrate
malfunction and early cross-sectional differential diagnosis
have been elusive thus far. We used repetitive learning and free
recall of abstract geometric patterns during functional magnetic
resonance imaging to assess episodic memory in older subjects
(ages 56-64 years) who sought first-time medical attention with
subjective memory complaints and were diagnosed with probable
Alzheimer's disease (NINCDS-ADRDA criteria; ages 51-67 years) or
major depressive disorder (DSM-IV; ages 50-65 years).
Contrasting healthy seniors or depressive patients with
Alzheimer's disease patients revealed superiority of hippocampal
activation. Contrasting Alzheimer's disease patients with
seniors showed bilateral prefrontal activity as a correlate of
futile compensation of episodic memory failure. Contrasting
patients who had major depressive disorder with seniors or
patients who had Alzheimer's disease showed bilateral activation
of the orbitofrontal cortex and the anterior cingulate.
Subjective memory complaints may be classified objectively and
very early with functional magnetic resonance imaging of
episodic memory in groups of patients with Alzheimer's disease
and depressive syndrome. This may facilitate drug trials with
evaluation of specific treatments, but further studies will be
needed to establish the differential diagnosis for the
individual patient.
PMID: 11921055 [PubMed - indexed for MEDLINE]
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13: Neurosci Lett. 2001 Nov 13;314(1-2):57-60. Related Articles, Links
Transcranial magnetic stimulation in
Alzheimer disease: motor cortex excitability and cognitive
severity.
Alagona G, Bella R, Ferri R, Carnemolla A, Pappalardo A,
Costanzo E, Pennisi G.
Department of Neurological Sciences, University of, Catania,
Italy
To study the possible changes of cortical excitability in the
Alzheimer disease (AD) by transcranial magnetic stimulation
(TMS) and to evaluate their eventual correlation with its stage
twenty-one AD patients and 18 normal controls underwent TMS.
Motor threshold, amplitudes of motor evoked potentials (MEPs),
central motor conduction time (CMCT) and silent period (SP) were
considered. The motor threshold in AD patients was lower than in
normal subjects with a significant correlation between the stage
of cognitive severity. The amplitude of MEPs was increased and
the SP duration was reduced in AD patients. No significant
differences were obtained for CMCT. These findings could suggest
a correlation between increased motor cortical excitability and
cognitive severity. Moreover, the increased cortical
excitability could represent a key to understand the mechanism
of AD and may have implication for novel treatment strategies.
PMID: 11698146 [PubMed - indexed for MEDLINE]
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14: Neurology. 2001 Sep 11;57(5):812-6. Related Articles, Links
Dissociation of regional activation in mild
AD during visual encoding: a functional MRI study.
Kato T, Knopman D, Liu H.
Center for Magnetic Resonance Research, Department of Radiology,
University of Minnesota, Minneapolis, USA.
OBJECTIVE: The authors studied mild patients with AD with a
visual learning paradigm to determine whether activations of
medial temporal regions on fMRI differ in AD compared to
nondemented individuals. BACKGROUND: Changes in activation
patterns of medial temporal lobe regions may serve as a biologic
marker of altered brain function early in the course of AD.
METHODS: The authors studied eight healthy young subjects, eight
late middle-age nondemented volunteers, and seven patients with
mild AD. All subjects underwent fMRI scanning in which they
viewed a set of geometric designs for 45 seconds. Changes in
blood flow were analyzed by comparing the prestimulus fMRI
signal with that present during the stimulus presentation.
RESULTS: Patients with AD, who had very poor recall of the
geometric designs subsequently, showed increased blood flow
(activation) during stimulus presentation only in a visual
association area. Both the young and older nondemented subjects,
all of whom had good recall of the designs, showed activations
during stimulus presentation of the right entorhinal cortex,
right supramarginal gyrus, right prefrontal regions, and left
anterior-inferior temporal lobe. The younger and older
nondemented subjects did not differ in fMRI activation patterns.
CONCLUSIONS: Failure of activation in AD of either temporal lobe
or prefrontal regions is consistent with established
clinical-pathologic correlations in AD. fMRI may be useful in
confirming a memory disorder diagnosis and also may be useful in
detecting individuals with incipient dysfunction in learning as
a result of disorders such as AD.
PMID: 11552009 [PubMed - indexed for MEDLINE]
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15: J Cogn Neurosci. 2000;12 Suppl 2:24-34. Related Articles, Links
Functional brain imaging of young,
nondemented, and demented older adults.
Buckner RL, Snyder AZ, Sanders AL, Raichle ME, Morris JC.
Howard Hughes Medical Institute and Department of Psychology,
Washington University, St. Louis, MO 63130, USA.
Brain imaging based on functional MRI (fMRI) provides a powerful
tool for characterizing age-related changes in functional
anatomy. However, between-population comparisons confront
potential differences in measurement properties. The present
experiment explores the feasibility of conducting fMRI studies
in nondemented and demented older adults by measuring
hemodynamic response properties in an event-related design. A
paradigm involving repeated presentation of sensory-motor
response trials was administered to 41 participants (14 young
adults, 14 nondemented older adults, and 13 demented older
adults). For half of the trials a single sensory-motor event was
presented in isolation and in the other half in pairs.
Hemodynamic response characteristics to the isolated events
allowed basic response properties (e.g., amplitude and variance)
between subject groups to be contrasted. The paired events
further allowed the summation properties of the hemodynamic
response to be characterized. Robust and qualitatively similar
activation maps were produced for all subject groups.
Quantitative results showed that for certain regions, such as in
the visual cortex, there were marked reductions in the amplitude
of the hemodynamic response in older adults. In other regions,
such as in the motor cortex, relatively intact response
characteristics were observed. These results suggest caution
should be exhibited in interpreting simple main effects in
response amplitude between subject groups. However, across all
regions examined, the summation of the hemodynamic response over
trials was highly similar between groups. This latter finding
suggests that, even if absolute measurement differences do exist
between subject groups, relative activation change should be
preserved. Designs that rely on group interactions between task
conditions, parametric manipulations, or group interactions
between regions should provide valuable data for making
inferences about functional-anatomic changes between different
populations.
PMID: 11506645 [PubMed - indexed for MEDLINE]
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16: Clin Neurophysiol. 2001 Aug;112(8):1436-41. Related Articles, Links
Motor cortex disinhibition in Alzheimer's
disease.
Liepert J, Bar KJ, Meske U, Weiller C.
Department of Neurology, Friedrich Schiller University, Jena,
Germany.
OBJECTIVES: To explore subclinical disturbances in the motor
cortex of patients with Alzheimer's disease (AD). METHODS: We
used transcranial magnetic stimulation in a paired pulse
technique to test intracortical inhibition (ICI) and
intracortical facilitation in mildly to moderately demented AD
patients with a normal neurological examination. Patients were
studied before and during treatment with the cholinesterase
inhibitor donepezil. RESULTS: AD patients had a reduced ICI
compared to an age-matched control group. The amount of
disinhibition correlated with the severity of dementia.
Treatment with 10 mg donepezil daily was associated with an
increase of ICI. CONCLUSIONS: The subclinical motor cortex
disinhibition in AD patients indicates a functional disturbance,
and is probably associated with a cholinergic deficit.
PMID: 11459683 [PubMed - indexed for MEDLINE]
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17: Neuroscience. 2001;104(3):667-76. Related Articles, Links
Remembering familiar people: the posterior
cingulate cortex and autobiographical memory retrieval.
Maddock RJ, Garrett AS, Buonocore MH.
Depaartment of Psychiatry, University of California Davis,
Sacramento 65817, USA.
Most functional imaging studies of memory retrieval investigate
memory for standardized laboratory stimuli. However, naturally
acquired autobiographical memories differ from memories of
standardized stimuli in important ways. Neuroimaging studies of
natural memories may reveal distinctive patterns of brain
activation and may have particular value in assessing clinical
disorders of memory. This study used functional magnetic
resonance imaging to investigate brain activation during
successful retrieval of autobiographical memories elicited by
name-cued recall of family members and friends. The caudal part
of the left posterior cingulate cortex was the most strongly
activated region and was significantly activated in all eight
subjects studied. Most subjects also showed significant
activation of the left anterior orbitomedial, anterior middle
frontal, precuneus, cuneus, and posterior inferior parietal
cortices, and the right posterior cingulate and motor
cortices.Our findings are consistent with prior studies showing
posterior cingulate cortex activation during autobiographical
memory retrieval. This region is also consistently activated
during retrieval of standardized memory stimuli when
experimental designs emphasizing successful retrieval are
employed. Our results support the hypothesis that the posterior
cingulate cortex plays an important role in successful memory
retrieval. The posterior cingulate cortex has strong reciprocal
connections with entorhinal and parahippocampal cortices.
Studies of early Alzheimer's disease, temporal lobectomy, and
hypoxic amnesia show that hypometabolism of the posterior
cingulate cortex is an early and prominent indicator of
pathology in these patients. Our findings suggest that
autobiographical memory retrieval tasks could be used to probe
the functional status of the posterior cingulate cortex in
patients with early Alzheimer's disease or at risk for that
condition.
PMID: 11440800 [PubMed - indexed for MEDLINE]
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18: Neuroreport. 2001 Jun 13;12(8):1649-52. Related Articles, Links
Preserved stimulus deviance detection in
Alzheimer's disease.
Pekkonen E, Jaaskelainen LP, Erkinjuntti T, Hietanen M,
Huotilainen M, Ilmoniemi RJ, Naatanen R.
Department of Neurology, University of Helsinki, and Medical
Engineering Centre, Helsinki University Central Hospital,
Finland.
Aging attenuates automatic auditory discrimination to duration
change, whereas frequency change detection is relatively
unimpaired in aging and in Alzheimer's disease (AD). Here we
studied with a whole-head magnetometer whether cortical auditory
discrimination to duration change as shown by magnetic mismatch
negativity (MMNm) response is impaired in AD. Twenty AD patients
with mild to moderate cognitive impairment and 18 age-matched
healthy subjects were monaurally presented a sequence of
frequent standard tones embedded with occasional deviants with
shorter duration. MMNm was significantly delayed in the left
hemisphere ipsilaterally to the ear stimulated in the patient
group, whereas the MMNm amplitudes over both hemispheres were
quite similar in both groups. This suggests that although MMNm
is delayed in the left hemisphere, the automatic discrimination
to duration change in the auditory cortex is not attenuated in
the early stages of AD.
PMID: 11409733 [PubMed - indexed for MEDLINE]
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19: Brain. 2001 Jun;124(Pt 6):1131-7. Related Articles, Links
Examination of motor output pathways in
patients with corticobasal ganglionic degeneration using
transcranial magnetic stimulation.
Valls-Sole J, Tolosa E, Marti MJ, Valldeoriola F, Revilla M,
Pastor P, Blesa R.
Unitat d'EMG, Neurology Service, Hospital Clinic, Universitat de
Barcelona, Villarroel, 170 Barcelona 08036, Spain.
The alien hand sign (AHS) is often encountered in patients with
corticobasal ganglionic degeneration (CBGD), revealing a
unilateral dysfunction of the motor system of unknown
pathophysiology. We examined the possibility of an abnormal
cortical representation of hand muscles in 10 patients with
probable CBGD and a prominent AHS. Cortical maps were obtained
from the responses to magnetic stimuli applied with a figure of
eight coil at an intensity of 110% above motor threshold. For
comparison, the same study was carried out in 10 normal
volunteers, eight patients with Parkinson's disease and eight
patients with Alzheimer's disease. AHS patients had a larger
extension of the cortical map to stimulation of the hemisphere
contralateral to the AHS in comparison with the ipsilateral
hemisphere. Furthermore, in six patients, focal stimulation of
the hemisphere ipsilateral to the AHS gave rise to ipsilateral
responses, delayed by a mean of 7.7 +/- 2.2 ms with respect to
those recorded in the same muscle to contralateral stimulation.
None of the other patients or control subjects had ipsilateral
responses. Our results indicate an enhanced excitability, or
reduced inhibition, of the motor area of the hemisphere
contralateral to the AHS. The delay of the ipsilateral responses
is compatible with a disinhibited transcallosal input.
PMID: 11353729 [PubMed - indexed for MEDLINE]
------------------------------------------------------------------------
20: Hum Brain Mapp. 2000 Aug;10(4):195-6. Related Articles, Links
Comment on:
* Hum Brain Mapp. 2000 Aug;10(4):197-203.
Perceptual priming and extrastriate cortex:
consensus and controversy.
Nyberg L.
Department of Psychology, Umea University, Sweden.
Publication Types:
* Comment
PMID: 10949056 [PubMed - indexed for MEDLINE]
------------------------------------------------------------------------
21: AJNR Am J Neuroradiol. 2000 Mar;21(3):524-31. Related Articles, Links
Functional MR imaging using a visually
guided saccade paradigm for comparing activation patterns in
patients with probable Alzheimer's disease and in cognitively
able elderly volunteers.
Thulborn KR, Martin C, Voyvodic JT.
Department of Radiology, MR Research Center, University of
Pittsburgh Medical Center, PA, USA.
BACKGROUND AND PURPOSE: Alzheimer's disease is associated with
progressive visuospatial dysfunction. This study used functional
MR (fMR) imaging with an eye movement paradigm to investigate
differences in visuospatial cognition between patients with
probable Alzheimer's disease (pAD) and cognitively able elderly
volunteers. METHODS: Using established, although imperfect,
clinical criteria, patients with pAD (n = 18) and cognitively
able elderly volunteers (n = 10) were selected for study. All
patients underwent echo-planar fMR imaging at 1.5 T. The
visually guided saccade paradigm consisted of alternating
periods (30 s) of central fixation and visually guided saccades
to a target appearing randomly along the horizontal meridian.
Activation maps were derived using a voxelwise t test, comparing
the signal intensities between the two steady-state conditions.
The activation patterns were characterized by Talairach
coordinates, activation volumes, and laterality ratios (LRs).
RESULTS: Statistically significant differences existed between
the activation patterns of the patients with pAD and those of
the volunteers. In contrast to the control group, a
left-dominant parietal activation pattern and enhanced
prefrontal cortical activation were observed in most patients
with pAD. CONCLUSION: Within the limitations of the imperfect
clinical standard of reference, the reduction in right parietal
activation producing the left-dominant LR for the intraparietal
sulcus may reflect the progressive dysfunction in spatial
attention associated with Alzheimer's disease, considering the
known parietal lobe involvement in this function and the
disease. The high specificity of a positive intraparietal sulcal
LR measured by fMR imaging may have a role in detecting and
monitoring Alzheimer's disease.
PMID: 10730646 [PubMed - indexed for MEDLINE]
------------------------------------------------------------------------
22: Dtsch Med Wochenschr. 1999 Dec 23;124(51-52):1577-81. Related Articles, Links
[Neurology. Therapeutic advances through
systems research and molecular biology]
[Article in German]
Hohlfeld R, Brandt T.
Institut fur Klinische Neuroimmunologie, Klinikum Grosshadern,
Ludwig Maximilians Universitat, Munchen.
PMID: 10664661 [PubMed - indexed for MEDLINE]
------------------------------------------------------------------------
23: Brain Res. 1999 Dec 11;850(1-2):179-88. Related Articles, Links
Regulation of GTPase and adenylate cyclase
activity by amyloid beta-peptide and its fragments in rat brain
tissue.
Soomets U, Mahlapuu R, Tehranian R, Jarvet J, Karelson E, Zilmer
M, Iverfeldt K, Zorko M, Graslund A, Langel U.
Department of Neurochemistry and Neurotoxicology, Arrhenius
Laboratories, Stockholm University, Sweden.
Modulation of GTPase and adenylate cyclase (ATP
pyrophosphate-lyase, EC 4.6.1.1) activity by Alzheimer's disease
related amyloid beta-peptide, A beta (1-42), and its shorter
fragments, A beta (12-28), A beta (25-35), were studied in
isolated membranes from rat ventral hippocampus and frontal
cortex. In both tissues, the activity of GTPase and adenylate
cyclase was upregulated by A beta (25-35), whereas A beta
(12-28) did not have any significant effect on the GTPase
activity and only weakly influenced adenylate cyclase. A beta
(1-42), similar to A beta (25-35), stimulated the GTPase
activity in both tissues and adenylate cyclase activity in
ventral hippocampal membranes. Surprisingly, A beta (1-42) did
not have a significant effect on adenylate cyclase activity in
the cortical membranes. At high concentrations of A beta (25-35)
and A beta (1-42), decreased or no activation of adenylate
cyclase was observed. The activation of GTPase at high
concentrations of A beta (25-35) was pertussis toxin sensitive,
suggesting that this effect is mediated by Gi/G(o) proteins.
Addition of glutathione and N-acetyl-L-cysteine, two well-known
antioxidants, at 1.5 and 0.5 mM, respectively, decreased A beta
(25-35) stimulated adenylate cyclase activity in both tissues.
Lys-A beta (16-20), a hexapeptide shown previously to bind to
the same sequence in A beta-peptide, and prevent fibril
formation, decreased stimulation of adenylate cyclase activity
by A beta (25-35), however, NMR diffusion measurements with the
two peptides showed that this effect was not due to interactions
between the two and that A beta (25-35) was active in a
monomeric form. Our data strongly suggest that A beta and its
fragments may affect G-protein coupled signal transduction
systems, although the mechanism of this interaction is not fully
understood.
PMID: 10629763 [PubMed - indexed for MEDLINE]
------------------------------------------------------------------------
24: J Neurol Sci. 1999 Nov 30;170(2):119-23. Related Articles, Links
Motor cortex inhibition is not impaired in
patients with Alzheimer's disease: evidence from paired
transcranial magnetic stimulation.
Pepin JL, Bogacz D, de Pasqua V, Delwaide PJ.
University Department of Neurology, CHR Citadelle, Bd du XIIeme
de Ligne, 1, 4000, Liege, Belgium.
Motor cortex excitability was studied by transcranial magnetic
stimulation (TMS) in 17 patients with Alzheimer's disease (AD).
Resting and active thresholds for TMS were significantly reduced
in AD patients compared to young and aged healthy subjects. The
maximum amplitude of the motor response evoked by TMS was also
significantly increased in AD patients. We have tested if these
changes are related to a modification of the short-lasting
intracortical inhibition of the motor cortex by paired
conditioning-test TMS. We found no significant differences
between AD patients and aged healthy subjects even if there is a
slight but significant difference between aged and young normal
subjects. We conclude that the modification of excitability of
the motor cortex does not result from an impaired intracortical
inhibition.
PMID: 10561527 [PubMed - indexed for MEDLINE]
------------------------------------------------------------------------
25: J Int Neuropsychol Soc. 1999 Jul;5(5):377-92. Related Articles, Links
Neuroanatomic substrates of semantic memory
impairment in Alzheimer's disease: patterns of functional MRI
activation.
Saykin AJ, Flashman LA, Frutiger SA, Johnson SC, Mamourian AC,
Moritz CH, O'Jile JR, Riordan HJ, Santulli RB, Smith CA, Weaver
JB.
Department of Psychiatry, Dartmouth Medical School, Lebanon, NH
03756, USA.
Impairment in semantic processing occurs early in Alzheimer's
disease (AD) and differential impact on subtypes of semantic
relations have been reported, yet there is little data on the
neuroanatomic basis of these deficits. Patients with mild AD and
healthy controls underwent 3 functional MRI auditory stimulation
tasks requiring semantic or phonological decisions
(match-mismatch) about word pairs (category-exemplar,
category-function, pseudoword). Patients showed a significant
performance deficit only on the exemplar task. On voxel-based
fMRI activation analyses, controls showed a clear activation
focus in the left superior temporal gyrus for the phonological
task; patients showed additional foci in the left dorsolateral
prefrontal and bilateral cingulate areas. On the semantic tasks,
predominant activation foci were seen in the inferior and middle
frontal gyrus (left greater than right) in both groups but
patients showed additional activation suggesting compensatory
recruitment of locally expanded foci and remote regions, for
example, right frontal activation during the exemplar task.
Covariance analyses indicated that exemplar task performance was
strongly related to signal increase in bilateral medial
prefrontal cortex. The authors conclude that fMRI can reveal
similarities and differences in functional neuroanatomical
processing of semantic and phonological information in mild AD
compared to healthy elderly, and can help to bridge cognitive
and neural investigations of the integrity of semantic networks
in AD.
PMID: 10439584 [PubMed - indexed for MEDLINE]
------------------------------------------------------------------------
26: J Neurol. 1997 May;244(5):304-7. Related Articles, Links
Magnetic stimulation in Alzheimer's
disease.
de Carvalho M, de Mendonca A, Miranda PC, Garcia C, Luis ML.
Department of Neurology, Hospital de Santa Maria, Lisbon,
Portugal.
Alzheimer's disease (AD) is a common cause of dementia in which
some clinical motor abnormalities have been described. We used
transcranial magnetic stimulation in order to test the
hypothesis that the change in the motor cortex might cause
modifications in motor excitability. Fourteen mildly to
moderately affected AD patients were compared with 11 controls
matched for age, height and sex. The motor evoked potential
threshold value for the relaxed abductor digiti minimi was lower
in the AD patients than in the control group for both left and
right hemispheres (P < 0.05). No statistically significant
difference was found comparing the left and the right
hemispheres thresholds in each population. The mean interside
threshold differences were small and not significantly different
between patients and controls. The spinal motor neuron
excitability, as evaluated by F/M and H/M waves amplitude
ratios, showed no difference between the groups, reinforcing the
motor cortex increased excitability hypothesis to explain this
difference. Degeneration of inhibitory gabaergic terminals might
be the basis for the increased cortical excitability in the
motor cortex of the Alzheimer patients; postsynaptic changes in
the GABAA receptors might also affect inhibitory gabaergic
transmission. The increased excitability found by transcranial
magnetic stimulation in the motor cortex is important for
understanding the emergence of seizures and myoclonus in this
disease.
PMID: 9178155 [PubMed - indexed for MEDLINE]
------------------------------------------------------------------------
27: Neuroreport. 1996 May 31;7(8):1365-8. Related Articles, Links
Alzheimer's disease affects parallel
processing between the auditory cortices.
Pekkonen E, Huotilainen M, Virtanen J, Naatanen R, Ilmoniemi RJ,
Erkinjuntti T.
Department of Psychology, University of Helsinki, Finland.
Auditory evoked magnetic fields (AEFs) were recorded from 11
patients with Alzheimer's disease (AD) and 11 age-matched
controls using the 122-channel whole-head magnetometer. Auditory
stimuli were monaurally presented with interstimulus intervals
(ISI) of 0.5 and 2.5 s in different blocks. The peak latencies
of P50m and N100m responses were significantly longer in AD
patients than in controls over the ipsilateral but not over the
contralateral auditory cortex with respect to the ear
stimulated. This finding suggests that parallel auditory
processing is impaired between the auditory cortices in AD
patients. The present MEG measurement might provide an objective
index to evaluate auditory dysfunction in AD.
PMID: 8856676 [PubMed - indexed for MEDLINE]
------------------------------------------------------------------------
28: J Neurol Sci. 1996 Jan;135(1):31-7. Related Articles, Links
Evaluation of the motor cortex by magnetic
stimulation in patients with Alzheimer disease.
Perretti A, Grossi D, Fragassi N, Lanzillo B, Nolano M,
Pisacreta AI, Caruso G, Santoro L.
Department of Clinical Neurophysiology, University of Naples,
Italy.
Motor evoked potentials (MEPs) from abductor pollicis brevis
(APB) and tibialis anterior (TA) muscles elicited by
transcranial magnetic stimulation of the motor cortex were
studied in 15 patients with Alzheimer disease (AD). An
abnormally higher MEP threshold in APB, frequently associated
with absence of the MEP in relaxed TA muscles, was found in 40%
of patients, almost all of them in the more severe stage of the
disease. The MEP amplitude and averaged MEP/MAP ratio were
reduced respectively by 20% and 26% in the APB muscle, and by
46.7% and 53.3% in the TA muscle. The less frequent prolongation
of the central conduction time (CCT) (20%) might reflect
preservation of the impulse propagation along the surviving
pyramidal fibers. In 63.6% of the patients the central silent
period (cSP) duration in the APB muscle was shortened; the mean
value was significantly different between patients and controls.
The results of this study suggest that loss and/or dysfunction
of motor cortex neurones, including pyramidal cells and
inhibitory interneurones may occur in AD patients before
clinical signs become apparent.
PMID: 8926493 [PubMed - indexed for MEDLINE]
------------------------------------------------------------------------
29: J Med Chem. 1995 Apr 28;38(9):1558-70. Related Articles, Links
In vitro muscarinic activity of
spiromuscarones and related analogs.
Wu ES, Griffith RC, Loch JT 3rd, Kover A, Murray RJ, Mullen GB,
Blosser JC, Machulskis AC, McCreedy SA.
Department of Chemistry and Biology, Fisons Pharmaceuticals,
Rochester, New York 14623, USA.
The cholinergic hypothesis of Alzheimer's disease suggests that
cholinergic agonists may have therapeutic potential for treating
the attendant memory deficits of the disease. As part of a
program aimed at preparing metabolically stable, nonquaternary
analogs of muscarone,
1-oxa-2,8-dimethyl-8-azaspiro[4.5]decan-3-one, 2a, and related
analogs have been synthesized and their in vitro muscarinic
activity evaluated. The synthetic strategy in the formation of
the 1-spiro[4.5]decan-3-one ring system of 2a involved
cyclization of the diol 4 in the presence of Nafion-Hg. The
spiromuscarone 2a was found to displace [3H]Oxo-M binding with a
Ki value of 7 nM. Affinities of the oxime and hydrazone analogs
of 2a were lower than 2a. The compounds in these series were
partial muscarinic agonists as demonstrated by stimulation of
phosphatidyl inositol hydrolysis assay, with 2a showing the
highest intrinsic intrinsic activity (60% as compared with
carbachol). The results from this study indicate that an exo
double bond at the C-3 position is essential for the receptor
binding.
PMID: 7739014 [PubMed - indexed for MEDLINE]
------------------------------------------------------------------------
30: West J Med. 1994 Sep;161(3):273-8. Related Articles, Links
Mapping human brain activity in vivo.
Mazziotta JC.
Department of Neurology, Reed Neurological Research Center, Los
Angeles, CA.
A wide range of structural and functional techniques now exists
to map the human brain in health and disease. These approaches
span the gamut from external tomographic imaging devices
(positron-emission tomography, single photon-emission computed
tomography, magnetic resonance imaging, computed tomography), to
surface detectors (electroencephalography,
magnetoencephalography, transcranial magnetic stimulation), to
measurements made directly on the brain's surface or beneath it
(intrinsic signal imaging, electrocorticography). The
noninvasive methods have been combined to provide unique and
previously unavailable insights into the macroscopic
organization of the functional neuroanatomy of human vision,
sensation, hearing, movement, language, learning, and memory.
All methods have been applied to patients with neurologic,
neurosurgical, and psychiatric disease and have provided a
rapidly expanding knowledge of the pathophysiology of diseases
such as epilepsy, cerebrovascular disease, neoplasms,
neurodegenerative diseases, mental illness, and addiction
states. In addition, these new methods have become a mainstay of
preoperative surgical planning and the monitoring of
pharmacologic or surgical (transplantation) interventions. Most
recently, the ability to observe the reorganization of the human
nervous system after acute injury, such as occurs with cerebral
infarction or head trauma, or in the course of a progressive
degenerative process such as Alzheimer's or Parkinson's disease,
may provide new insights and methods in the rapidly expanding
field of neurorehabilitation. Our newfound ability to generate
maps and databases of human brain development, maturation, skill
acquisition, aging, and disease states is both an exciting and
formidable task.
Publication Types:
* Review
* Review, Tutorial
PMID: 7975566 [PubMed - indexed for MEDLINE]
------------------------------------------------------------------------
31: J Med Chem. 1994 Aug 19;37(17):2774-82. Related Articles, Links
Design, synthesis, and neurochemical
evaluation of
2-amino-5-(alkoxycarbonyl)-3,4,5,6-tetrahydropyridines and
2-amino-5-(alkoxycarbonyl)-1,4,5,6-tetrahydropyrimidines as M1
muscarinic receptor agonists.
Dunbar PG, Durant GJ, Rho T, Ojo B, Huzl JJ 3rd, Smith DA,
el-Assadi AA, Sbeih S, Ngur DO, Periyasamy S, et al.
Department of Medicinal and Biological Chemistry, College of
Pharmacy, University of Toledo, Ohio 43606.
Four regioisomers of
2-amino-(methoxycarbonyl)-3,4,5,6-tetrahydropyridine (2a-5a)
were synthesized as the racemates to evaluate the utility of
exocyclic amidines in the development of novel agonists for M1
muscarinic receptors. Of the four regioisomers, only racemic
2-amino-5-(methoxycarbonyl)-3,4,5,6-tetrahydropyridine (4a;
CDD-0075-A) displayed high affinity (IC50 = 10 +/- 3.0 microM)
and activity at muscarinic receptors coupled to PI metabolism in
the rat cortex (260 +/- 4.5% stimulation above basal levels at
100 microM). A series of
2-amino-5-(alkoxycarbonyl)-3,4,5,6-tetrahydropyridines then was
synthesized for further evaluation as M1 agonists. Only the
propargyl derivative (4d) retained substantial agonist activity
(120 +/- 14% at 100 microM) in this series. On the basis of the
activity of the 5-(alkoxycarbonyl)-1,4,5,6-
tetrahydropyrimidines (1a and 1d) and the
2-amino-5-(alkoxycarbonyl)-3,4,5,6-tetrahydropyridines, the
corresponding cyclic guanidine derivatives were synthesized and
tested. 2-Amino-5-(methoxycarbonyl)-1,4,5,6-tetrahydropyrimidine
(7a) displayed a modest affinity for muscarinic receptors in the
CNS (22 +/- 5.3 microM) and an ability to stimulate PI turnover
in rat cerebral cortex (81 +/- 16% at 100 microM). The propargyl
derivative (7d) also had modest binding affinity (31 +/- 15
microM) and high activity (150 +/- 8.5% at 100 microM), as
expected based on the activity of propargyl esters of
1,4,5,6-tetrahydropyrimidine and
2-amino-3,4,5,6-tetrahydropyridine. Computational chemical
studies revealed five distinct minimum-energy conformations for
1a, (R)-4a, and 7a, and three for 1d, (R)-4d, and 7d, each with
a unique orientation of the ester moiety. Each of the five
conformations for 1a could be superimposed upon a unique
conformer of (R)-4a and 7a, suggesting that the compounds
interact with muscarinic receptors in a similar fashion. Taken
together, the data indicate the general utility of amidine
systems as suitable replacements for the ammonium group of
acetylcholine in developing ligands with activity at M1
muscarinic receptors in the central nervous system. Such
compounds might be useful in the treatment of patients with
Alzheimer's disease.
PMID: 8064804 [PubMed - indexed for MEDLINE]
------------------------------------------------------------------------
32: Cerebrovasc Brain Metab Rev. 1992 Spring;4(1):1-27. Related Articles, Links
PET correlates of normal and impaired
memory functions.
Heiss WD, Pawlik G, Holthoff V, Kessler J, Szelies B.
Max-Planck-Institut fur neurologische Forschung, Koln, Germany.
To date, positron emission tomography (PET) has been the only
technology for the quantitative imaging of the changes of
regional cerebral glucose (rCMRGl) or oxygen metabolism and
blood flow (rCBF) associated with psychophysical stimulation and
with the performance of mental tasks. So far, the majority of
studies performed in healthy subjects demonstrated activation
patterns involving not only certain limbic structures, most of
all hippocampus, amygdala, parahippocampus, and cingulate, but
also temporal, parietal, and occipital association cortex,
depending on the applied paradigm. Indeed, the closest
correlation between regional metabolism and memory test scores
was found in mesiotemporal structures during the performance of
memory tasks. Metabolic or CBF studies also seem to indicate
that memorizing strategies may differ among individuals. PET was
repeatedly used to investigate metabolic and/or blood flow
abnormalities in patients with various amnestic syndromes. In
cases with uni- or bilateral lesions of mesiotemporal
structures, caused by surgery, herpes simplex encephalitis, or
permanent ischemic, anoxic, or toxic damage, disturbances of
metabolism and blood flow typically extended far beyond the
morphological defects detected by computed tomography or
magnetic resonance. In acute transient global amnesia, CBF and
metabolism were decreased bilaterally in the mesiotemporal
lobes, where hypometabolism persisted for some time, while
higher values were observed in thalamus and some cortical areas.
Diencephalic lesions causing Korsakoff's syndrome were
associated with decreased rCMRGl in the hippocampal formation,
upper brainstem, cingulate, and thalamus. Discrete thalamic
infarcts caused amnesia and metabolic depression in the
morphologically intact ipsilateral thalamus and in various
projection areas of the infarcted nuclei. In ischemic forebrain
lesions, amnestic deficits could be related to involvement of
the anterior cingulate and of basal cholinergic nuclei. A large
number of pathologies are diffusely spread out in the brain and
affect partially or predominantly structures in memory
processing. This holds true especially in the various dementias
where memory disturbances are a consistent and often leading
feature. Notably, Alzheimer's disease can be distinguished from
other dementias by its characteristic pattern of metabolic
dysfunction, with the most prominent changes occurring in
parietotemporal and frontal association cortex whose residual
metabolism is related to the severity of the disease. Therefore,
activation studies using paradigms involving memory functions
enhance that typical pattern. Only in the activated state is
metabolism of mesiotemporal structures significantly correlated
with the performance in memory tests. Other dementias also
affect some of the distributed memory networks, with
Huntington's disease suggesting a role of the striatum in memory
processing.(ABSTRACT TRUNCATED AT 400 WORDS)
Publication Types:
* Review
* Review, Academic
PMID: 1562450 [PubMed - indexed for MEDLINE]
------------------------------------------------------------------------
33: Acupunct Electrother Res. 1992;17(2):107-48. Related Articles, Links
Common factors contributing to intractable
pain and medical problems with insufficient drug uptake in areas
to be treated, and their pathogenesis and treatment: Part I.
Combined use of medication with acupuncture, (+) Qi gong
energy-stored material, soft laser or electrical stimulation.
Omura Y, Losco BM, Omura AK, Takeshige C, Hisamitsu T,
Shimotsuura Y, Yamamoto S, Ishikawa H, Muteki T, Nakajima H, et
al.
Heart Disease Research Foundation, New York.
Most frequently encountered causes of intractable pain and
intractable medical problems, including headache, post-herpetic
neuralgia, tinnitus with hearing difficulty, brachial essential
hypertension, cephalic hypertension and hypotension, arrhythmia,
stroke, osteo-arthritis, Minamata disease, Alzheimer's disease
and neuromuscular problems, such as Amyotrophic Lateral
Sclerosis, and cancer are often found to be due to co-existence
of 1) viral or bacterial infection, 2) localized
microcirculatory disturbances, 3) localized deposits of heavy
metals, such as lead or mercury, in affected areas of the body,
4) with or without additional harmful environmental
electro-magnetic or electric fields from household electrical
devices in close vicinity, which create microcirculatory
disturbances and reduced acetylcholine. The main reason why
medications known to be effective prove ineffective with
intractable medical problems, the authors found, is that even
effective medications often cannot reach these affected areas in
sufficient therapeutic doses, even though the medications can
reach the normal parts of the body and result in side effects
when doses are excessive. These conditions are often difficult
to treat or may be considered incurable in both Western and
Oriental medicine. As solutions to these problems, the authors
found some of the following methods can improve circulation and
selectively enhance drug uptake: 1) Acupuncture, 2) Low pulse
repetition rate electrical stimulation (1-2 pulses/second), 3)
(+) Qi Gong energy, 4) Soft lasers using Ga-As diode laser or
He-Ne gas laser, 5) Certain electro-magnetic fields or rapidly
changing or moving electric or magnetic fields, 6) Heat or
moxibustion, 7) Individually selected Calcium Channel Blockers,
8) Individually selected Oriental herb medicines known to reduce
or eliminate circulatory disturbances. Each method has
advantages and limitations and therefore the individually
optimal method has to be selected. Applications of (+) Qi Gong
energy stored paper or cloth every 4 hours, along with effective
medications, were often found to be effective, as Qigongnized
materials can often be used repeatedly, as long as they are not
exposed to rapidly changing electric, magnetic or
electro-magnetic fields. Application of (+) Qi Gong
energy-stored paper or cloth, soft laser or changing electric
field for 30-60 seconds on the area above the medulla oblongata,
vertebral arteries or endocrine representation area at the tail
of pancreas reduced or eliminated microcirculatory disturbances
and enhanced drug uptake.(ABSTRACT TRUNCATED AT 400 WORDS)
Publication Types:
* Clinical Trial
PMID: 1353650 [PubMed - indexed for MEDLINE]
------------------------------------------------------------------------
34: J Neurol Neurosurg Psychiatry. 1991 May;54(5):443-8. Related Articles, Links
Posterior cortical dementia with alexia:
neurobehavioural, MRI, and PET findings.
Freedman L, Selchen DH, Black SE, Kaplan R, Garnett ES, Nahmias
C.
Department of Psychology, Mississauga Hospital, Ontario, Canada.
A progressive disorder of relatively focal but asymmetric
biposterior dysfunction is described in a 54 year old right
handed male. Initial clinical features included letter-by-letter
alexia, visual anomia, acalculia, mild agraphia, constructional
apraxia, and visuospatial compromise. Serial testing
demonstrated relentless deterioration with additional
development of transcortical sensory aphasia, Gerstmann's
tetrad, and severe visuoperceptual impairment. Amnesia was not
an early clinical feature. Judgment, personality, insight, and
awareness remained preserved throughout most of the clinical
course. Extinction in the right visual field to bilateral
stimulation was the sole neurological abnormality. Early CT was
normal and late MRI showed asymmetrical bioccipitoparietal
atrophy with greater involvement of the left hemisphere. Results
from positron emission tomography (PET) showed bilaterally
asymmetric (left greater than right) occipitotemporoparietal
hypometabolism. The metabolic decrement was strikingly
asymmetric with a 50% reduction in glucose consumption confined
to the left occipital cortex. The picture of
occipitotemporoparietal compromise verified by MRI, PET, and
neurobehavioural testing would be unusual for such degenerative
dementias as Alzheimer's (AD) and Pick's disease, although
atypical AD with predominant occipital lobe involvement cannot
be excluded. This case supports the concepts of posterior
cortical dementia (PCD) as a clinically distinct entity and for
the first time documents its corresponding metabolic deficit
using PET.
PMID: 1865209 [PubMed - indexed for MEDLINE]
------------------------------------------------------------------------
35: Eur Neurol. 1991;31(4):259-69. Related Articles, Links
Mapping of event-related potentials to
auditory and visual odd-ball paradigms in patients affected by
different forms of dementia.
Onofrj M, Gambi D, Del Re ML, Fulgente T, Bazzano S, Colamartino
P, Malatesta G.
Istituto di Clinica Neurologica, Universita G. D'Annunzio,
Chieti, Italia.
The paper reports the results of recordings and maps of
event-related potentials (ERPs) in patients with Alzheimer's
disease (AD), progressive supranuclear palsy (PSP) and in
subjects affected by dementia in multiple sclerosis (MS). ERPs
were recorded from 19 scalp electrode derivations using both
visual and acoustic paradigms. In 43% of AD patients, ERPs were
normal; in 20%, although present, ERP components were delayed,
while in the other 37% none of the N2 and P3 peaks could be
recorded, because of abnormal topography of potentials on the
scalp. In patients with PSP, the normal ERP sequence was not
identified. In patients with MS delayed ERPs (50%), abnormal
topography of ERPs (30%) and absence of ERPs (20%) were
observed. The follow-up of AD patients showed a progressive
alteration of ERPs. ERP topography alterations were observed in
AD, PSP and MS patients with poorest cognitive performances.
PMID: 1868869 [PubMed - indexed for MEDLINE]