Towards a cognitive neuroscience of self-awareness.

Self-awareness is a pivotal component of conscious experience. It is correlated with a paralimbic network of medial prefrontal/anterior cingulate and medial parietal/posterior cingulate cortical "hubs" and associated regions. Electromagnetic and transmitter manipulation have demonstrated that the network is not an epiphenomenon but instrumental in generation of self-awareness. Thus, transcranial magnetic stimulation (TMS) targeting the hubs impedes different aspects of self-awareness with a latency of 160ms. The network is linked by ∼40Hz oscillations and regulated by dopamine. The oscillations are generated by rhythmic GABA-ergic inhibitory activity in interneurons with an extraordinarily high metabolic rate. The hubs are richly endowed with interneurons and therefore highly vulnerable to disturbed energy supply. Consequently, deficient paralimbic activity and self-awareness are characteristic features of many disorders with impaired oxygen homeostasis. Such disorders may therefore be treated unconventionally by targeting interneuron function.

Perinatal hypoxic-ischemic brain damage and intraventricular hemorrhage. A pathogenetic model.

Perinatal hypoxic-ischemic brain damage and intraventricular hemorrhage (IVH) are important causes of death and neurologic and intellectual dysfunction. Both lesions are related to perinatal asphyxia, and the aim of our review is to establish a comprehensive pathogenetic model. Our previous finding that cerebral blood flow is pressure-passive in perinatal distress is crucial, as periods of hypertension and hypotension alternate in the distressed infant. In hypertension, transmural pressure increases in the capillaries, leading to edema and, in premature infants, eventual rupture of vessels and IVH. Intraventricular hemorrhage induces vasospasm and ischemia. Ischemia is the direct result of hypotension. Cerebral blood flow studies performed a few hours after birth with subsequent examinations at one year of age point to a decisive effect of neonatal ischemia on subsequent development.

Focal cerebral hypoperfusion in children with dysphasia and/or attention deficit disorder.

The neural mechanisms involved in learning disorders are largely unknown. We studied three-dimensional regional cerebral blood flow (rCBF) in 13 children with dysphasia and/or attention deficit disorder (ADD), using xenon 133 inhalation and emission computed tomography. The rCBF distribution was abnormal in both hemispheres in all patients, as compared with the mean CBF distribution of nine normal children. Regions of hypoperfusion and, by inference, low metabolic activity were predominantly seen in the periventricular white matter and in border zones between major arterial territories. In patients with dysphasia, parts of both perisylvian regions were hypoperfused, and object-naming tasks failed to produce an increased flow in relevant cortical regions. Patients with different dysphasic syndromes appeared to have different patterns of rCBF. All 11 patients with ADD had hypoperfusion in the white matter of the frontal lobes and seven also in the caudate nuclei region. Methylphenidate hydrochloride increased perfusion in the central region, including the mesencephalon and the basal ganglia, and decreased perfusion of motor and primary sensory cortical areas. The location of hypoperfused structures in cognitive disorders of childhood is consistent with a role for an early hypoxic-ischemic event in their origin.

Striatal dysfunction in attention deficit and hyperkinetic disorder.

We have previously reported that periventricular structures are hypoperfused in attention deficit and hyperactivity disorder (ADHD). This study has expanded the number of patients, who were divided into two groups: six patients with pure ADHD, and 13 patients with ADHD in combination with other neurologic symptoms. By using xenon 133 inhalation and emission tomography, the regional cerebral blood flow distribution was determined and compared with a control group. Striatal regions were found to be hypoperfused and, by inference, hypofunctional in both groups. This hypoperfusion was statistically significant in the right striatum in ADHD, and in both striatal regions in ADHD with other neuropsychologic and neurologic symptoms. The primary sensory and sensorimotor cortical regions were highly perfused. Methylphenidate increased flow to striatal and posterior periventricular regions, and tended to decrease flow to primary sensory regions. Low striatal activity, partially reversible with methylphenidate, appears to be a cardinal feature in ADHD.

Nitric oxide does not act as a mediator coupling cerebral blood flow to neural activity following somatosensory stimuli in rats.

The possible role of nitric oxide (NO) on vibrissa-stimulated increase of regional cerebral cerebral blood flow (rCBF) and cerebral metabolic rate of glucose (rCMRglu) was investigated in conscious Wistar rats by using an inhibitor of NO synthase, NG-nitro-L-arginine (NOLAG) at a concentration of 30 mg/kg. In vivo autoradiography distribution with 14C-iodoantipyrine and 14C-deoxyglucose in two separate series showed CBF of 174% of control and CMRglu of 196% of control in the primary sensory cortex opposite the stimulated side in saline treated control animals. Similar increases were found in NOLAG-treated animals. Furthermore, NOLAG did not change either basal CMRglu or CMRO2. The findings suggest, that NO is not involved in coupling flow to the increased metabolism accompanying physiological sensory stimuli.

Observations on the perioperative management of patients undergoing the Maze procedure.

In addition to the usual measures that constitute optimal perioperative care after cardiac surgery, the Maze procedure demands several other measures because of certain complications that are unique to this particular operation. These complications include preoperative conditions such as amiodarone therapy, thromboembolism, diastolic dysfunction of the left ventricle, and associated valvular heart disease, as well as intraoperative differences that include multiple atriotomies and excision of both atrial appendages. The most common postoperative complications are atrial arrhythmias, excessive fluid retention, and pulmonary complications. In this article, we outline our own approach to the perioperative care of patients undergoing the Maze procedure.

Current status of the Maze procedure for the treatment of atrial fibrillation.

Since the first patient underwent the Maze procedure on September 25, 1987, 346 patients have undergone this operation for the treatment of atrial fibrillation. The procedure was designed as an open-heart operation performed through a median sternotomy. It underwent 2 major modifications relatively early in the series, evolving into the so-called Maze-III procedure, which has been used exclusively since April 16, 1992. Since that time, the Maze-III procedure has been adapted to allow it to be done by minimally invasive techniques. In addition, we recently performed the entire procedure in 2 patients without the use of cardiopulmonary bypass. The operative mortality rate has remained at 2% to 3%. This includes patients undergoing concomitant high-risk cardiac surgical procedures and all re-do cases. The overall success rate in curing atrial fibrillation has been 99%. The procedure itself has been shown to cause no permanent damage to the sinus node. The left atrium has been documented to function long-term postoperatively in 93% of patients and the right atrium functions in 99% of patients. The Maze-III procedure remains the surgical procedure of choice for the treatment of medically refractory atrial fibrillation.

The Maze-III procedure combined with valve surgery.

Previous studies have suggested that the Maze procedure is not as effective in controlling atrial fibrillation when the arrhythmia is associated with significant valvular heart disease. In this study, we evaluate our own results in 83 patients who underwent 96 valve procedures in combination with the Maze-III procedure. Our results indicate that the Maze-III procedure is just as safe and effective in controlling atrial fibrillation associated with valvular heart disease as it is in controlling atrial fibrillation not associated with valvular heart disease.

Neonatal seizures associated with cerebral lesions shown by magnetic resonance imaging.

AIM: To determine the diagnostic potential of magnetic resonance imaging (MRI) in neonatal seizures; to elucidate the aetiology, timing, and prognosis of the cerebral lesions detected. METHODS: Thirty one term neonates with clinical seizures underwent ultrasonography between days 1-7 (mean 2.5 days) and a high field spin-echo MRI scan on days 1-30 (mean 8.1 days), both of which were repeated at 3 months of age. Routine investigation excluded, as far as possible, infection, haematological, and metabolic-toxic causes as causes of the neonatal seizures. RESULTS: Brain abnormality was demonstrated by MRI in 68% of infants and ultrasonographically in 10%. Diffuse brain lesions (present in 29%) were associated with high mortality (58%) and morbidity (42%), whatever the aetiology. In contrast to a better short term prognosis for neonates with focal lesions where no infants died, 33% had a handicap, and the rest were normal at a mean follow up age of 2 1/2 years. Cerebral lesions were presumed to have antepartum origin in 43% of cases. Seizure aetiology was considered to be hypoxic-ischaemic in 35%, haemorrhagic in 26%, metabolic disturbances and cerebral dysgenesis in 16% and unknown in 23%. CONCLUSIONS: MRI detected a remarkably high incidence of brain lesions in neonatal seizures. Almost half of these were of prenatal origin and pathogenesis may essentially be attributed to hypoxic and/or haemodynamic causes.

Visual cortex reactivity in sedated children examined with perfusion MRI (FAIR).

Sleeping and sedated children can respond to visual stimulation with a decrease in blood oxygenation level dependent (BOLD) functional MRI signal response. The contribution of metabolic and hemodynamic parameters to this inverse signal response is incompletely understood. It has been hypothesized that it is caused by a relatively greater increase of oxygen consumption compared to rCBF (regional cerebral blood flow) increase. We studied the rCBF changes during visual stimulation in four sedated children, aged 4-71 months, and four alert adults, with an arterial water spin labeling technique (FAIR) and BOLD fMRI in a 1.5T MR scanner. In the children, FAIR signal decreased by a mean of 0.96% (range 0.77-1.05) of the baseline periods of the non-selective images, while BOLD signal decreased by 2.03% (range 1.99-2.93). In the adults, FAIR and BOLD signal increased by 0.88% (range 0.8-0.99) and 2.63% (range 1.99-2.93), respectively. Thus, in the children, an rCBF increase could not be detected by perfusion MRI, but indications of a FAIR signal decrease were found. An rCBF decrease in the primary visual cortex during stimulation has not been reported previously, but it is a possible explanation for the negative BOLD response. Future studies will have to address if this response pattern is a consequence of age or sleep/sedation.