Alicja Lerner

Regional cerebral blood flow correlates of the severity of writer's cramp symptoms

UNLABELLED Writers cramp is a type of idiopathic focal dystonia with incompletely understood pathophysiology. Recent studies provide evidence that one element might be a sensory processing defect. We performed a PET study with O(15) H(2)O to find out in which brain areas activity correlates with the severity of writers cramp symptoms. METHODS We studied 10 patients with writers cramp and 10 age- and gender-matched control subjects. There were seven conditions, each repeated twice: rest, writing, tapping with index finger for 2, 3, 4, and 5 min. For each scan, we obtained EMG recordings from the flexor digitorum superficialis (FDS), extensor indicis proprius (EIP) muscles, and a subjective score of severity of dystonia. Scans were realigned, normalized, smoothed, and analyzed using SPM99. Analysis included both intra- and intergroup comparisons and a correlation analysis where we used EMG recordings and subjective dystonia score as covariates. RESULTS Random effect analysis of the writing task showed overactivity of the primary sensory cortex and no significant underactivity. Correlation analysis of dystonia patients showed activation of SI when we used the subjective dystonia score as a covariate, and activation of both the SI and primary motor cortex when the normalized EMG score of FDS was used. CONCLUSION While some overactivity of MI is not surprising, overactivity of SI is more dramatic and suggests a primary deficit in processing sensory feedback. Writers cramp may arise in part as a dysfunction of sensory circuits, which causes defective sensorimotor integration resulting in co-contractions of muscles and overflow phenomena.

Small effect of dopamine release and no effect of dopamine depletion on [18F]fallypride binding in healthy humans

Molecular imaging has been used to estimate both drug‐induced and tonic dopamine release in the striatum and most recently extrastriatal areas of healthy humans. However, to date, studies of drug‐induced and tonic dopamine release have not been performed in the same subjects. This study performed positron emission tomography (PET) with [18F]fallypride in healthy subjects to assess (1) the reproducibility of [18F]fallypride and (2) both D‐amphetamine‐induced and α‐methyl‐p‐tyrosine (AMPT)‐induced changes in dopamin release on [18F]fallypride binding in striatal and extrastriatal areas. Subjects underwent [18F]fallypride PET studies at baseline and following oral D‐amphetamine administration (0.5 mg/kg) and oral AMPT administration (3 g/70 kg/day over 44 h). Binding potential (BP) (BPND) of [18F]fallypride was calculated in striatal and extrastriatal areas using a reference region method. Percent change in regional BPND was computed and correlated with change in cognition and mood. Test–retest variability of [18F]fallypride was low in both striatal and extrastriatal regions. D‐Amphetamine significantly decreased BPND by 8–14% in striatal subdivisions, caudate, putamen, substantia nigra, medial orbitofrontal cortex, and medial temporal cortex. Correlation between change in BPND and verbal fluency was seen in the thalamus and substantia nigra. In contrast, depletion of endogenous dopamine with AMPT did not effect [18F]fallypride BPND in both striatum and extrastriatal regions. These findings indicate that [18F]fallypride is useful for measuring amphetamine‐induced dopamine release, but may be unreliable for estimating tonic dopamine levels, in striatum and extrastriatal regions of healthy humans. Synapse 62:399–408, 2008. Published 2008 Wiley‐Liss, Inc.

Neuroimaging of neuronal circuits involved in tic generation in patients with Tourette syndrome

Objective: To identify brain regions generating tics in patients with Tourette syndrome using sleep as a baseline. Methods: We used [15O]H2O PET to study nine patients with Tourette syndrome and nine matched control subjects. For patients, conditions included tic release states and sleep stage 2; and for control subjects, rest states and sleep stage 2. Results: Our study showed robust activation of cerebellum, insula, thalamus, and putamen during tic release. Conclusion: The network of structures involved in tics includes the activated regions and motor cortex. The prominent involvement of cerebellum and insula suggest their involvement in tic initiation and execution.

Olfactory pathogenesis of idiopathic Parkinson disease revisited

Idiopathic Parkinson disease (PD) is traditionally considered a movement disorder with hallmark lesions located in the substantia nigra pars compacta (SNpc). However, recent histopathological studies of some PD cases suggest the possibility of a multisystem disorder which progresses in a predictable sequence as described in Braaks staging criteria. The disease process starts in the dorsal motor nucleus of the vagus (dmX) and anterior olfactory nucleus and bulb, and from there, spreads through the brainstem nuclei to ultimately reach the SNpc, which then presents as symptomatic PD. In this article, we would like to revisit the olfactory pathogenesis of PD based on Braaks staging system and review anatomical pathways supporting such a possibility. We also suggest some biomarkers for early stages of PD. Additionally, we present and discuss the possibility that a prion‐like process underlies the neurodegenerative changes in PD.

Involvement of Insula and Cingulate Cortices in Control and Suppression of Natural Urges

The physiology of control and suppression of natural urges is not well understood. We used [(15)O]H(2)O positron-emission tomography imaging to identify neural circuits involved in suppression of spontaneous blinking as a model of normal urges. Suppression of blinking was associated with prominent activation of bilateral insular-claustrum regions, right more than left; activation was also found in bilateral anterior cingulate cortex (ACC), supplementary motor areas, and the face area of the primary motor cortex bilaterally. These results suggest a central role for the insula possibly together with ACC in suppression of blinking.

Increased midbrain gray matter in Tourette's syndrome

To investigate cerebral structure in Tourettes syndrome (TS).

Decreased Neurokinin-1 (Substance P) Receptor Binding in Patients with Panic Disorder: Positron Emission Tomographic Study with [18F]SPA-RQ

BACKGROUND Positron emission tomography (PET) can localize and quantify neurokinin-1 (NK(1)) receptors in brain using the nonpeptide antagonist radioligand, [(18)F]SPA-RQ. We sought to determine if patients with panic disorder have altered density of NK(1) receptors in brain because of their history of recurrent panic attacks. We also sought to determine if a drug-induced panic attack releases substance P in brain, as measured by decreased binding of [(18)F]SPA-RQ. METHODS Positron emission tomography scans with [(18)F]SPA-RQ were performed in 14 patients with panic disorder and 14 healthy subjects. Of these two groups, 7 patients and 10 healthy subjects were scanned twice, once at baseline and once after injection of doxapram, a drug that induces panic attacks. RESULTS NK(1) receptor binding in patients (n = 14) compared with that in healthy subjects (n = 14) was significantly decreased by 12% to 21% in all brain regions. Doxapram effectively produced panic attacks in 6 of 7 patients with panic disorder but only 2 of 10 healthy subjects. Doxapram caused no significant change of [(18)F]SPA-RQ binding in either patients or healthy subjects. CONCLUSIONS Although induction of a panic attack has no significant effect on [(18)F]SPA-RQ binding to NK(1) receptors, patients with panic disorder have widespread reduction of NK(1) receptor binding in brain.

Remission of Gilles de la Tourette Syndrome after Heat-Induced Dehydration

Heat has been reported to exert variable effects on people with Gilles de la Tourette syndrome (TS). At age 24 years, a 32-year-old right-handed man with TS experienced a marked reduction in tics for two years after undergoing dehydration by entering a hot tub at 103°F (39.4°C) to 104°F (40.0°C) for 3 to 4 hours. On the Yale Global Tic Severity Scale (YGTSS) he scored 55 seven months before dehydration and 13 one month after dehydration. An intense heat exposure and dehydration led to an apparent remission in tics. The remission continued without the use of prescribed or nonprescribed medications or substances for two years until tics returned in the worst ever exacerbation after a tetanus immunization. The heat exposure may have altered at least temporarily his thermostat for normal heat-loss mechanisms through dopaminergic pathways from the anterior hypothalamus to the basal ganglia and the substantia nigra. Whether or not that mechanism or some other mechanism relevant to the heat exposure and/or dehydration is at play, the sudden and marked improvement in his tics needs further attention. Prospective testing of the heat and dehydration effect on tics should be pursued.