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Biomedical subjects

John F Stein

Publications and source records attributed to John F Stein.

At least 19 recordsLinked to original sources
PubMed2006

Identifying cardiorespiratory neurocircuitry involved in central command during exercise in humans.

For almost one hundred years, the exact role of human brain structures controlling the cardiorespiratory response to exercise ('central command') has been sought. Animal experiments and functional imaging studies have provided clues, but the underlying electrophysiological activity of proposed relevant neural sites in humans has never been measured. In this study, local field potentials were directly recorded in a number of 'deep' brain nuclei during an exercise task designed to dissociate the exercise from peripheral feedback mechanisms. Several patient groups had electrodes implanted sterotaxically for the treatment of movement disorder or chronic pain. Fast Fourier transform analysis was applied to the neurograms to identify the power of fundamental spectral frequencies. Anticipation of exercise resulted in increases in heart rate, blood pressure and ventilation. The greatest neural changes were found in the periaqueductal grey area (PAG) where anticipation of exercise was accompanied by an increase of 43% in the power of the 12-25 Hz frequency band (P = 0.007). Exercise increased the activity by 87% compared to rest (P = 0.006). Changes were also seen in the 60-90 Hz band when anticipation or exercise increased power by 32% (P = 0.006) and 109% (P < 0.001), respectively. In the subthalamic nucleus there was a reduction in the power of the beta frequency during both anticipation (7.6 +/- 0.68% P = 0.001) and exercise (17.3 +/- 0.96% P < 0.001), whereas an increase was seen with exercise only at higher frequencies (93 +/- 1.8% P = 0.007). No significant changes were seen in the globus pallidus during anticipation of exercise. We provide direct electrophysiological evidence highlighting the PAG as an important subcortical area in the neural circuitry of the cardiorespiratory response to exercise, since stimulation of this structure is known to alter blood pressure in awake humans.

Adult↗
PubMed2006

Auditory event-related potentials differ in dyslexics even when auditory psychophysical performance is normal.

Developmental dyslexia is characterized by a phonological processing deficit and impaired low-level auditory processing may contribute to this problem. However, this remains controversial because not all dyslexic individuals show psychophysical deficits on auditory processing tasks; hence it has been argued that auditory processing deficits are not a causal factor in dyslexia. Because behavioral psychophysical tasks include both bottom-up processing and top-down strategies, dyslexics' successful coping strategies may positively influence their performance on auditory behavioral measures. Therefore we have studied whether dyslexics who perform adequately on auditory psychophysical tasks nevertheless show electrophysiological evidence of impaired auditory processing. We compared auditory event-related mismatch negativity (MMN) potentials to frequency modulated (FM) tones at 5, 20 and 240 Hz between dyslexic adults and controls. Groups were matched for age, cognitive ability and psychophysical FM detection thresholds. The dyslexic group showed significantly smaller MMNs in the 20 Hz FM condition in both the early (150-300 ms, P=0.010) and late (300-500 ms, P=0.049) time frames. A 2-way ANOVA showed a significant group by FM rate interaction (P=0.012). There were no significant differences between the groups in the 5 Hz or 240 Hz conditions. The magnitude of the 20 Hz FM MMN correlated with the degree of discrepancy between cognitive and literacy skills (0.66, P=0.003) in the entire group. Thus, even among compensated dyslexics with above-average cognitive abilities and adequate performance on auditory psychophysical tasks, the MMN responses of some dyslexic adults were found to be abnormal.

Adult↗
PubMed2006

Membrane fatty acids, reading and spelling in dyslexic and non-dyslexic adults.

Increasing evidence implicates functional deficiencies or imbalances of omega-3 and omega-6 fatty acids in dyslexia. The associations between literacy skills and omega-3 and omega-6 fatty acid status were examined. 32 dyslexics and 20 controls completed standardised tests of reading and spelling and gave venous blood samples for analysis of the polar lipid fatty acid composition of red blood cell (RBC) membranes. Relationships between literacy skills and omega-3 and omega-6 concentrations were examined using rank-order correlations. Better word reading was associated with higher total omega-3 concentrations in both dyslexic and control groups. In dyslexic subjects only, reading performance was negatively associated with the ratio of arachidonic acid/eicosapentaenoic acid (ARA/EPA) and with total omega-6 concentrations. There were no significant differences in membrane fatty acid levels between the dyslexic and control subjects. However, the finding that omega-3 status was directly related to reading performance irrespective of dyslexia supports a dimensional view of this condition, and our results also suggest that it is the omega-3/omega-6 balance that is particularly relevant to dyslexia.

Adult↗
PubMed2006

A dominant bursting electromyograph pattern in dystonic conditions predicts an early response to pallidal stimulation.

Although chronic pallidal deep brain stimulation (DBS) is effective in the treatment of medically intractable dystonia, there is no way of predicting the variations in clinical outcome, partly due to our limited understanding of the pathophysiological mechanisms underlying this condition. We recorded electromyographic (EMG) activity from the most severely affected muscle groups in seven dystonia patients before and after pallidal DBS. Patient EMG recordings could be classified into two groups: one consisting of patients who at rest demonstrated a dominant low frequency component of activity on power spectral analysis (ranging from 2 to 5 Hz), and one group in which this dominant pattern was absent. Early postoperative improvements (within 2-3 days) were observed in the former group, whereas the latter group benefited more gradually (over several months). Analysis of EMG activity may provide a sensitive means of identifying dystonic patients who are likely to be most responsive to functional neurosurgical intervention.

Action Potentials↗
PubMed2006

Stimulating the human midbrain to reveal the link between pain and blood pressure.

The periaqueductal grey area (PAG) in the midbrain is an important area for both cardiovascular control and modulation of pain. However, the precise relationship between pain and blood pressure is unknown. We prospectively studied 16 patients undergoing deep brain stimulation of the rostral PAG for chronic pain. Pre-operatively, post-operatively, and at 1 year, pain scores were assessed using both visual analogue scores and the McGill Pain Questionnaire. Patients were tested post-operatively to determine whether electrical stimulation of the PAG would modulate blood pressure. We found that the degree of analgesia induced by deep brain stimulation of the rostral PAG in man is related to the magnitude of reduction in arterial blood pressure. We found that this relationship is linear and is related to reduced activity of the sympathetic nervous system. Thus stimulation of the PAG may partly control pain by reducing sympathetic activity as predicted by William James over a century ago.

Adult↗
PubMed2006

Physiological and harmonic components in neural and muscular coherence in Parkinsonian tremor.

OBJECTIVE: To differentiate physiological from harmonic components in coherence analysis of the tremor-related neural and muscular signals by comparing power, cross-power and coherence spectra. METHODS: Influences of waveform, burst-width and additional noise on generating harmonic peaks in the power, cross-power and coherence spectra were studied using simulated signals. The local field potentials (LFPs) of the subthalamic nucleus (STN) and the EMGs of the contralateral forearm muscles in PD patients with rest tremor were analysed. RESULTS: (1) Waveform had significant effect on generating harmonics; (2) noise significantly decreased the coherence values in a frequency-dependent fashion; and (3) cross-spectrum showed high resistance to harmonics. Among six examples of paired LFP-EMG signals, significant coherence appeared at the tremor frequency only, both the tremor and double tremor frequencies and the double-tremor frequency only. CONCLUSIONS: In coherence analysis of neural and muscular signals, distortion in waveform generates significant harmonic peaks in the coherence spectra and the coherence values of both physiological and harmonic components are modulated by extra noise or non-tremor related activity. SIGNIFICANCE: The physiological or harmonic nature of a coherence peak at the double tremor frequency may be differentiated when the coherence spectra are compared with the power and in particular the cross-power spectra.

Electric Stimulation↗
PubMed2006

The physiologically modulated electrode potentials at the depth electrode-brain interface in humans.

To study the modulated electrical potential specifically related to the electrode-brain interface (EBI) in deep brain stimulation (DBS) under physiological condition, we quantitatively identified the physiologically modulated electrode potentials by decomposing the local field potentials (LFPs) recorded from 11 patients (18 electrodes in four different brain regions) who underwent DBS, and correlated them with simultaneously recorded physiological signals of blood pressure (BP) and respiration. Results showed that electrode potentials were modulated by BP and respiration and could be detected as a specific component of the compound LFP signals with a mean (+/-S.D.) amplitude of 6.9+/-1.7 microV. The detection rate and amplitude of the modulated electrode potentials were independent from brain regions and neurological disorders. The current approach can be used to study the changes in properties of the EBI under physiological condition and to investigate the effects of the EBI on the 'crossing' current of either the neural signals to be recorded or the electrical pulses for neurostimulation.

Blood Pressure↗
PubMed2006

Pedunculopontine nucleus electric stimulation alleviates akinesia independently of dopaminergic mechanisms.

The symptom of Parkinson's disease that is most disabling and difficult to treat is akinesia. We have previously shown that low-frequency stimulation of the pedunculopontine nucleus can alleviate such akinesia in a macaque rendered Parkinsonian using 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine. Here, we have extended that study to show that adding stimulation of the pedunculopontine nucleus to levodopa treatment in this Parkinsonian monkey increased its motor activity significantly more than levodopa alone. This additivity suggests that pedunculopontine nucleus stimulation may improve movement by acting at a site downstream from where levodopa therapy affects the basal ganglia.

Animals↗
PubMed2006

The chromosome 6p22 haplotype associated with dyslexia reduces the expression of KIAA0319, a novel gene involved in neuronal migration.

Dyslexia is one of the most prevalent childhood cognitive disorders, affecting approximately 5% of school-age children. We have recently identified a risk haplotype associated with dyslexia on chromosome 6p22.2 which spans the TTRAP gene and portions of THEM2 and KIAA0319. Here we show that in the presence of the risk haplotype, the expression of the KIAA0319 gene is reduced but the expression of the other two genes remains unaffected. Using in situ hybridization, we detect a very distinct expression pattern of the KIAA0319 gene in the developing cerebral neocortex of mouse and human fetuses. Moreover, interference with rat Kiaa0319 expression in utero leads to impaired neuronal migration in the developing cerebral neocortex. These data suggest a direct link between a specific genetic background and a biological mechanism leading to the development of dyslexia: the risk haplotype on chromosome 6p22.2 down-regulates the KIAA0319 gene which is required for neuronal migration during the formation of the cerebral neocortex.

Animals↗
PubMed2006

A processing speed deficit in dyslexic adults? Evidence from a peg-moving task.

Developmental dyslexia is diagnosed when literacy skills are not commensurate with a person's general cognitive ability and education. While the most common difficulty found in dyslexia is poor phonological processing, many dyslexics are reported to be clumsy, with poor handwriting, suggesting that there may be a motor deficit in dyslexia. To establish whether the motor difficulties described in dyslexic children persist into adulthood, we tested 18 dyslexic adults and 22 control participants on Annett's peg-moving task. The dyslexic participants performed significantly slower than control adults on the peg-moving task with their dominant hands (p=0.004). Furthermore, response times (RTs) during tasks testing component literacy skills correlated with peg-moving ability in the dominant hand in the entire group (orthographic r=0.448, p=0.005; phonological r=0.383, p=0.025). These results indicate that a motor speed deficit in dyslexia may not be simply a sign of developmental delay, but may persist into adulthood. Furthermore, motor speed may be related to the speed at which literacy information is processed.

Adult↗
PubMed2006

Different mechanisms may generate sustained hypertonic and rhythmic bursting muscle activity in idiopathic dystonia.

Despite that deep brain stimulation (DBS) of the globus pallidus internus (GPi) is emerging as the favored intervention for patients with medically intractable dystonia, the pathophysiological mechanisms of dystonia are largely unclear. In eight patients with primary dystonia who were treated with bilateral chronic pallidal stimulation, we correlated symptom-related electromyogram (EMG) activity of the most affected muscles with the local field potentials (LFPs) recorded from the globus pallidus electrodes. In 5 dystonic patients with mobile involuntary movements, rhythmic EMG bursts in the contralateral muscles were coherent with the oscillations in the pallidal LFPs at the burst frequency. In contrast, no significant coherence was seen between EMG and LFPs either for the sustained activity separated out from the compound EMGs in those 5 cases, or in the EMGs in 3 other cases without mobile involuntary movements and rhythmic EMG bursts. In comparison with the resting condition, in both active and passive movements, significant modulation in the GPi LFPs was seen in the range of 8-16 Hz. The finding of significant coherence between GPi oscillations and rhythmic EMG bursts but not sustained tonic EMG activity suggests that the synchronized pallidal activity may be directly related to the rhythmic involuntary movements. In contrast, the sustained hypertonic muscle activity may be represented by less synchronized activity in the pallidum. Thus, the pallidum may play different roles in generating different components of the dystonic symptom complex.

Adult↗
PubMed2006

Balancing and pointing tasks in dyslexic and control adults.

Developmental dyslexia may affect as much as 15% of the population, but the aetiology of the disorder is still being debated. The cerebellar theory of dyslexia proposes that cerebellar dysfunction could lead to the myriad of symptoms seen in dyslexic individuals, both in literacy and non-literacy domains. The cerebellum is crucial to the fluent performance of motor skills. Previous studies have found that dyslexic children are worse than control children on certain motor and balancing tasks. Here the performance of 28 dyslexic compared to 26 control adults on rapid pointing and balancing measures, tasks which are thought to reflect cerebellar function, was investigated. There were no significant differences between the dyslexic and control participants on the balancing tasks or when the speed and accuracy of pointing were analysed separately. However, when the speed and accuracy of pointing were combined, the dyslexic participants showed poorer performance than the controls (p = 0.045). Furthermore, there were significant relationships between performance on the pointing task and literacy skills, and regression analysis showed that the error and speed of pointing contributed significantly to the variance in literacy skill. The implications for the role of the cerebellum and processing speed in dyslexia are discussed.

Adolescent↗
PubMed2006

Controlling the heart via the brain: a potential new therapy for orthostatic hypotension.

OBJECTIVE: Electrical stimulation of the midbrain is known to influence blood pressure in animals. In humans, it is used for the treatment of chronic neuropathic pain. Our aim was to assess whether orthostatic hypotension can be successfully treated with deep brain stimulation of the periventricular/periaqueductal gray areas in humans. METHODS: We recruited 11 patients who had chronic neuropathic pain and who had undergone implantation of a deep brain stimulator in the periventricular/periaqueductal gray areas. Patients were divided into three groups depending on whether they had orthostatic hypotension (one patient), mild orthostatic intolerance (five patients), or no orthostatic intolerance (five patients). Postoperatively, we continuously recorded blood pressure and heart rate with stimulation off and on and in both sitting and standing positions. From these values, we derived the blood pressure changing rate. Using autoregressive modeling techniques, we calculated changes in low- and high-frequency power spectra of heart rate and baroreflex sensitivity. RESULTS: Electrical stimulation reduced the decrease in systolic blood pressure on standing from 28.2 to 11.1% in one patient with orthostatic hypotension (P < 0.001). In the mild orthostatic intolerance group, an initial drop in systolic blood pressure of 15.4% was completely reversed (P < 0.001). There were no side effects in the remaining group. These changes were accompanied by increases in the blood pressure changing rate, the baroreflex sensitivity, and the baseline (sitting) low-frequency power of the RR interval, but not the high-frequency power. CONCLUSION: Electrical stimulation of the human periventricular/periaqueductal gray areas can reverse orthostatic hypotension. The cause seems to be an increase in sympathetic outflow and in baroreflex sensitivity. This has important implications for future therapies.

Adult↗
PubMed2006

Use of surface electromyography to assess and select patients with idiopathic dystonia for bilateral pallidal stimulation.

OBJECT: The object of this study was to identify a preoperative physiological index by using surface electromyography (EMG) signals that would correlate with clinical outcome in dystonic patients following bilateral pallidal stimulation. METHODS: In 14 patients with spasmodic torticollis, generalized dystonia, and myoclonic dystonia, surface EMG signals were recorded from the most affected muscle groups. Although the dystonia affected different body segments, the EMG signals in all patients could be decomposed into bursting and sustained components. Subsequently, a ratio of the EMG amplitude was calculated between the two components and then correlated with clinical outcome. Patients who experienced rapid improvement following bilateral pallidal stimulation had a significantly higher EMG ratio compared with those who did not. Furthermore, a significant correlation was found between the EMG ratio and clinical improvement during the 12-month period following pallidal stimulation. CONCLUSIONS: The authors concluded that surface EMG studies could be used to predict the clinical outcome of and to select patients for pallidal stimulation for dystonia.

Adult↗
PubMed2005

Deep brain stimulation for the alleviation of post-stroke neuropathic pain.

Our aim was to asses the efficacy of deep brain stimulation in post-stroke neuropathic pain. Since 2000, 15 patients with post-stroke intractable neuropathic pain were treated with deep brain stimulation of the periventricular gray area (PVG), sensory thalamus (Ventroposterolateral nucleus-VPL) or both. Pain was assessed using both a visual analogue scale and the McGill's pain questionnaire. VAS scores show a mean improvement of 48.8% (SD 8.6%). However, there is a wide variation between patients. This study demonstrates that it is an effective treatment in 70% of such patients.

Deep Brain Stimulation↗
PubMed2005

Deep brain stimulation can regulate arterial blood pressure in awake humans.

The periaqueductal grey matter is known to play a role in cardiovascular control in animals. Cardiovascular responses to electrical stimulation of the periventricular/periaqueductal grey matter were measured in 15 awake human study participants following implantation of deep brain stimulating electrodes for treatment of chronic pain. We found that stimulation of the ventral periventricular/periaqueductal grey matter caused a mean reduction in systolic blood pressure of 14.2+/-3.6 mmHg in seven patients and stimulation of the dorsal periventricular/periaqueductal grey matter caused a mean increase of 16.7+/-5.9 mmHg in six patients. A comparison between ventral and dorsal electrodes demonstrated significant differences (P<0.05). These changes were accompanied by analogous changes in diastolic blood pressure, pulse pressure, maximum dP/dt but not in the time interval between each R wave on the electrocardiogram.

Adult↗
PubMed2005

Implicit motor learning deficits in dyslexic adults.

Children with developmental dyslexia fail to develop age-appropriate reading skills despite adequate intelligence and education. It has been suggested that dyslexics' various literacy, sensory and motor difficulties may be related to impaired cerebellar function. As the cerebellum is involved in motor learning, we measured serial reaction time performance in 40 adults (21 controls, 19 dyslexics). Dyslexic subjects performed comparably to controls during the randomly-ordered reaction time blocks, indicating that the dyslexics were as able as controls to make appropriate stimulus-response associations. However, the dyslexics failed to show the reaction time reduction that the control group showed during the repeated sequences (p = 0.018) and there was a significant group by condition effect when comparing the last two blocks of the sequence condition with the first two blocks of the final random condition (p = 0.008). Furthermore, there was a significant difference between good and poor readers on the degree of learning during the task (p = 0.015). This suggests that some dyslexics may suffer from an implicit motor learning deficit, which could generalize to non-motor learning.

Adult↗