The auditory system of monkeys includes a large number of interconnected subcortical nuclei and cortical areas. At subcortical levels, the structural components of the auditory system of monkeys resemble those of nonprimates, but the organization at cortical levels is different. In monkeys, the ventral nucleus of the medial geniculate complex projects in parallel to a core of three primary-like auditory areas, AI, R, and RT, constituting the first stage of cortical processing. These areas interconnect and project to the homotopic and other locations in the opposite cerebral hemisphere and to a surrounding array of eight proposed belt areas as a second stage of cortical processing. The belt areas in turn project in overlapping patterns to a lateral parabelt region with at least rostral and caudal subdivisions as a third stage of cortical processing. The divisions of the parabelt distribute to adjoining auditory and multimodal regions of the temporal lobe and to four functionally distinct regions of the frontal lobe. Histochemically, chimpanzees and humans have an auditory core that closely resembles that of monkeys. The challenge for future researchers is to understand how this complex system in monkeys analyzes and utilizes auditory information.

https://www.pnas.org/content/pnas/97/22/11793.full.pdf

Subdivisions of auditory cortex and processing streams in primates

Bradykinesia means slowness of movement and is one of the cardinal manifestations of Parkinson's disease. Weakness, tremor and rigidity may contribute to but do not fully explain bradykinesia. We argue that bradykinesia results from a failure of basal ganglia output to reinforce the cortical mechanisms that prepare and execute the commands to move. The cortical deficit is most apparent in midline motor areas. This leads to particular difficulty with self-paced movements, prolonged reaction times and abnormal pre-movement EEG activity. Movements are often performed with normally timed EMG bursts but the amount of EMG activity is underscaled relative to the desired movement parameters. There are also abnormalities in sensory scaling and sensorimotor integration. The brain appears to be able to compensate to some degree for the basal ganglia deficit. There is overactivity in the lateral premotor areas during task performance and movements can be speeded by giving sensory cues. Attention to movement is also beneficial. However, we propose that the engagement of compensatory processes may also lead to reduced performance in other tasks. For example, patients' problems in performing more than one task at the same time could result from lack of sufficient resources both to compensate for their basal ganglia deficit and to run two tasks simultaneously. Surgical therapies are unlikely to work solely by normalizing basal ganglia output to that seen in healthy individuals. It seems more plausible that surgery removes an interfering signal that allows more efficient compensation by other structures.

Pathophysiology of bradykinesia in parkinson's disease

Objective—To describe a clock drawing task (CLOX) designed to elicit executive impairment and discriminate it from non-executive constructional failure. Subjects—90 elderly subjects were studied (45 elderly and well persons from the independent living apartments of a continuing care retirement community and 45 patients with probable Alzheimer’s disease). The clock drawing performance of elderly patients was compared with that of 62 young adult controls. Methods—Subjects received the CLOX, an executive test (EXIT25), and the mini mental state examination (MMSE). The CLOX is divided into an unprompted task that is sensitive to executive control (CLOX1) and a copied version that is not (CLOX2). Between rater reliability (27 subjects) was high for both subtests. Results—In elderly subjects, CLOX subscores correlated strongly with cognitive severity (CLOX1: r=˛0.83 v the EXIT25; CLOX2:r=0.85vthe MMSE). EXIT25 and MMSE scores predicted CLOX1 scores independently of age or education (F(4,82)=50.7, p<0.001; R 2 =0.71). The EXIT25 accounted for 68% of CLOX1 variance. Only the MMSE significantly contributed to CLOX2 scores (F(4,72)= 57.2, p<0.001; R 2 =0.74). CLOX subscales discriminated between patients with Alzheimer’s disease and elderly controls (83.1% of cases correctly classified; Wilkes’ lambda=0.48, p<0.001), and between Alzheimer’s disease subgroups with and without constructional impairment (91.9% of cases correctly classified; Wilkes’ lambda=0.31, p<0.001). Conclusions—The CLOX is an internally consistent measure that is easy to administer and displays good inter-rater reliability. It is strongly associated with cognitive test scores.The pattern of CLOX failures may discriminate clinical dementia subgroups. (J Neurol Neurosurg Psychiatry 1998;64:588‐594)

https://jnnp.bmj.com/content/jnnp/64/5/588.full.pdf

CLOX: an executive clock drawing task

A distributed model of the human arterial tree including all main systemic arteries coupled to a heart model is developed. The one-dimensional (1-D) form of the momentum and continuity equations is solved numerically to obtain pressures and flows throughout the systemic arterial tree. Intimal shear is modeled using the Witzig-Womersley theory. A nonlinear viscoelastic constitutive law for the arterial wall is considered. The left ventricle is modeled using the varying elastance model. Distal vessels are terminated with three-element windkessels. Coronaries are modeled assuming a systolic flow impediment proportional to ventricular varying elastance. Arterial dimensions were taken from previous 1-D models and were extended to include a detailed description of cerebral vasculature. Elastic properties were taken from the literature. To validate model predictions, noninvasive measurements of pressure and flow were performed in young volunteers. Flow in large arteries was measured with MRI, cerebral flow with ultrasound Doppler, and pressure with tonometry. The resulting 1-D model is the most complete, because it encompasses all major segments of the arterial tree, accounts for ventricular-vascular interaction, and includes an improved description of shear stress and wall viscoelasticity. Model predictions at different arterial locations compared well with measured flow and pressure waves at the same anatomical points, reflecting the agreement in the general characteristics of the "generic 1-D model" and the "average subject" of our volunteer population. The study constitutes a first validation of the complete 1-D model using human pressure and flow data and supports the applicability of the 1-D model in the human circulation.

/pdf/validation-of-a-one-dimensional-model-of-the-systemic-1wtkdon8he.pdf

Validation of a one-dimensional model of the systemic arterial tree.

Using functional MRI (fMRI), we have studied the changes induced by the performance of a complex sequential motor task in the cortical areas of six akinetic patients with Parkinson's disease and six normal subjects. Compared with the normal subjects, the patients with Parkinson's disease exhibited a relatively decreased fMRI signal in the rostral part of the supplementary motor area (SMA) and in the right dorsolateral prefrontal cortex, as previously shown in PET studies. Concomitantly, the same patients exhibited a significant bilateral relative increase in fMRI signal in the primary sensorimotor cortex, lateral premotor cortex, inferior parietal cortex, caudal part of the SMA and anterior cingulate cortex. These fMRI data confirm that the frontal hypoactivation observed in patients with Parkinson's disease is restricted to the rostral part of the SMA and to the dorsolateral prefrontal cortex. These results also show that, apart from the lateral premotor and parietal cortices, increased fMRI signals can be found in other cortical motor areas of these patients, including the posterior SMA, the anterior cingulate cortex and the primary sensorimotor cortices, which are then likely to participate in the same putative attempt by the dopamine-denervated brain to recruit parallel motor circuits in order to overcome the functional deficit of the striatocortical motor loops.

/pdf/cortical-motor-reorganization-in-akinetic-patients-with-3zbxhhp1de.pdf

Cortical motor reorganization in akinetic patients with Parkinson's disease: A functional MRI study

• We have measured with single-photon emission tomography the regional cerebral blood flow changes that occurred in the supplementary motor areas and in the primary sensory motor areas during sequential finger-to-thumb opposition movements of the right hand in seven akinetic patients with Parkinson's disease and in nine normal volunteers. Parkinsonian patients were studied before ("off" condition) and after a subcutaneous injection of apomorphine hydrochloride which was able to switch them "on" (on condition). In normal volunteers and parkinsonian patients in the on condition, regional cerebral blood flow significantly increased in the supplementary motor areas and in the contralateral primary sensory motor cortex but not in the ipsilateral primary sensory motor cortex. On the contrary, no significant regional cerebral blood flow change was observed in these areas in parkinsonian patients in the off condition. These results support the hypothesis that a functional cortical motor area deafferentation is involved in the pathophysiological makeup of akinesia and that this abnormality is reversed by dopaminergic drugs.

Supplementary and Primary Sensory Motor Area Activity in Parkinson's Disease: Regional Cerebral Blood Flow Changes During Finger Movements and Effects of Apomorphine

A global mathematical model of the cerebral circulation in man

Background Collateral circulatory pathways are considered the primary determinant of cerebral hemodynamics in patients with obstructive lesions of the internal carotid arteries (ICaAs). However, the hemodynamic effects of the diameter of the anterior communicating artery (ACoA) have never been assessed quantitatively in humans. Methods and Results Two different mathematical models were used to simulate changes affecting blood pressures and flows in cerebral arteries as a function of ACoA diameter and ICaA stenoses or occlusions. Small changes in ACoA diameter were found to have marked hemodynamic effects when they occurred within the range of 0.4 to 1.6 mm, a situation observed in 80% of the cases. Outside this range, changes in ACoA diameter had no effect. Simulated pressure drops through a stenotic ICaA were consistent with those observed. They were found to depend on the degrees of the stenoses in both ICaAs and on ACoA diameter according to a simple equation. Pressure reserve in the middle and anterio...

Effects of Anterior Communicating Artery Diameter on Cerebral Hemodynamics in Internal Carotid Artery Disease A Model Study

Hemodynamic role of the circle of Willis in stenoses of internal carotid arteries. An analytical solution of a linear model

Regional cerebral blood flow was investigated using single photon emission computed tomography and xenon-133 intravenous injection in six patients with dementia of the Alzheimer type (DAT) with atypical focal clinical presentation, and in 20 age-matched healthy volunteers The patients had a progressive and preponderant cognitive deficit and a focal hypoperfusion that correlated with the neuropsychological findings, whereas the average flow did not significantly differ from that of controls The assessment of concordant haemodynamic and neuropsychological focal abnormalities could be useful in the diagnosis of atypical cases of DAT

https://jnnp.bmj.com/content/jnnp/50/12/1602.full.pdf

Jean-Pierre Marc-Vergnes

Papers

Supplementary and Primary Sensory Motor Area Activity in Parkinson's Disease: Regional Cerebral Blood Flow Changes During Finger Movements and Effects of Apomorphine

A global mathematical model of the cerebral circulation in man

Effects of Anterior Communicating Artery Diameter on Cerebral Hemodynamics in Internal Carotid Artery Disease A Model Study

Hemodynamic role of the circle of Willis in stenoses of internal carotid arteries. An analytical solution of a linear model

Focal cerebral hypoperfusion and selective cognitive deficit in dementia of the Alzheimer type.