Mark Schram Christensen

Restoration of autoregulation of cerebral blood flow by hypocapnia

DURING RECENT YEARS, a state of cerebral vasomotor paralysis has been demonstrated in foca2Zy diseased brain tissue in patients with apoplexy and intracranial tumors. 14 In these vasoparalytic areas there is a loss of autoregulation normally the cerebral blood flow is independent of the arterial blood pressure within wide limits and a loss of the normal response to changed arterial carbon dioxide tension (PaCOz) vasodilation during increased PaCOz and vasoconstriction during decreased PaCOz. Moreover, in some patients with apoplexy or intracranial tumors it has been observed that the vasomotor function also may be affected in nonfocal parts of the diseased hemisphere. Here, an impaired autoregulation but a preserved reaction to changes ofthe PaCOz was observed. 2-6 This nonfocal loss of autoregulation has been called global, as it was expected that a loss of autoregulation would also be present in the contralateral “nondiseased” hemisphere. It was also predicted that the global loss of autoregulation might be restored by hypocapnia.6 A restoration of autoregulation by hypocapnia might be of essential importance for the possible beneficial effect of the therapeutic use of hyperventilation in patients with intracranial diseases, as will be further commented on in the Discussion. In the present study the autoregulation has been examined in the nondiseased hemisphere of patients with apoplexy or intracranial tumors at different levels of PaCOz to test the abovementioned predictions. patients were studied under general anesthesia induced by 300 mg. of thiopental sodium and 30 mg. of d-tubocurarine chloride and maintained with oxygen and nitrous oxide (1:2). Relaxation was maintained with repeated doses of 5 to 10 mg. d-tubocurarine chloride. Regional c e r e b r a l blood P o w ( r C B F ) measurements were performed in the nondiseased hemisphere (contralateral to the focal lesion) in all patients. After stabilization of PaCOz at about the patient’s own level as recorded during spontaneous respiration before anesthesia, 2 flow measurements were carried out at intervals of fifteen minutes. The first was made during normotension and the second during hypertension induced by infusion of angiotensin (Hypertensin@). Thereafter the patient was hyperventilated, and following stabilization of the PaCOz at about 25 mm. Hg (after forty-five to sixty minutes ) , 2 more measurements were taken during normotension and hypertension. The 133Xe intracarotid injection method was used for the rCBF measurements and the flow was determined in 35 regions of the nondiseased hemisphere. This method has been described in detail p r e v i ~ u s l y ~ ~ ~ ~ * and shall be only briefly summarized here. A small polyethylene catheter was placed into the internal carotid artery by means of the Seldinger technique. Then, 2 to 3 mc. of 133Xe dissolved in 3 ml. of isotonic saline were injected rapidly (one to two seconds) through the catheter into the internal carotid artery. The clear-

Premotor cortex modulates somatosensory cortex during voluntary movements without proprioceptive feedback

Movement perception relies on sensory feedback, but the involvement of efference copies remains unclear. We investigated movements without proprioceptive feedback using ischemic nerve block during fMRI in healthy humans, and found preserved activation of the primary somatosensory cortex. This activation was associated with increased interaction with premotor cortex during voluntary movements, which demonstrates that perception of movements relies in part on predictions of sensory consequences of voluntary movements that are mediated by the premotor cortex.

Brain correlates of aesthetic expertise: A parametric fMRI study

Several studies have demonstrated that acquired expertise influences aesthetic judgments. In this paradigm we used functional magnetic resonance imaging (fMRI) to study aesthetic judgments of visually presented architectural stimuli and control-stimuli (faces) for a group of architects and a group of non-architects. This design allowed us to test whether level of expertise modulates neural activity in brain areas associated with either perceptual processing, memory, or reward processing. We show that experts and non-experts recruit bilateral medial orbitofrontal cortex (OFC) and subcallosal cingulate gyrus differentially during aesthetic judgment, even in the absence of behavioural aesthetic rating differences between experts and non-experts. By contrast, activity in nucleus accumbens (NAcc) exhibits a differential response profile compared to OFC and subcallosal cingulate gyrus, suggesting a dissociable role between these regions in the reward processing of expertise. Finally, categorical responses (irrespective of aesthetic ratings) resulted in expertise effects in memory-related areas such as hippocampus and precuneus. These results highlight the fact that expertise not only modulates cognitive processing, but also modulates the response in reward related brain areas.

Is the Prefrontal Cortex Necessary for Establishing Cognitive Sets

There is evidence from neuroimaging that the prefrontal cortex may be involved in establishing task set activity in advance of presentation of the task itself. To find out whether it plays an essential role, we examined patients with unilateral lesions of the rostral prefrontal cortex. They were first instructed as to whether to perform a spatial or a verbal working memory task and then given spatial and verbal items after a delay of 4–12 s. The patients showed an increase in switch costs, making more errors by repeating what they had done on the previous trial. They were able to establish regional task set activity during the instruction delay, as evidenced by sustained changes in the blood oxygenation level-dependent signal in caudal frontal regions. However, in contrast to healthy controls, they were less able to maintain functional connectivity among the surviving task-related brain regions, as evidenced by reduced correlations between them during instruction delays. The results suggest that the left rostral prefrontal cortex is indeed required for establishing a cognitive set but that the essential function is to support the functional connectivity among the task-related regions.

An fMRI study of the neural correlates of graded visual perception

The neural correlates of clearly perceived visual stimuli have been reported previously in contrast to unperceived stimuli, but it is uncertain whether intermediate or graded perceptual experiences correlate with different patterns of neural activity. In this study, the subjective appearance of briefly presented visual stimuli was rated individually by subjects with respect to perceptual clarity: clear, vague or no experience of a stimulus. Reports of clear experiences correlated with activation in a widespread network of brain areas, including parietal cortex, prefrontal cortex, premotor cortex, supplementary motor areas, insula and thalamus. The reports of graded perceptual clarity were reflected in graded neural activity in a network comprising the precentral gyrus, intraparietal sulcus, basal ganglia and the insula. In addition, the reports of vague experiences demonstrated unique patterns of activation. Different degrees of perceptual clarity were reflected both in the degree to which activation was found within parts of the network serving a clear conscious percept, and additional unique activation patterns for different degrees of perceptual clarity. Our findings support theories proposing the involvement of a widespread network of brain areas during conscious perception.

Cerebral activation is correlated to regional atrophy of the spinal cord and functional motor disability in spinal cord injured individuals.

Recovery of function following lesions in the nervous system requires adaptive changes in surviving circuitries. Here we investigate whether changes in cerebral activation are correlated to spinal cord atrophy and recovery of functionality in individuals with incomplete spinal cord injury (SCI). 19 chronic SCI individuals and 7 age-comparable controls underwent functional magnetic resonance imaging (fMRI) while performing rhythmic dorsiflexion of the ankle. A significant negative correlation was found between the activation in the ipsilateral motor (M1) and bilateral premotor cortex (PMC) on one hand and the functional ability of the SCI participants measured by the clinical motor score on the other. There was no significant correlation between activation in any other cerebral area and the motor score. Activation in ipsilateral somatosensory cortex (S1), M1 and PMC was negatively correlated to the width of the spinal cord in the left-right direction, where the corticospinal tract is located, but not in the antero-posterior direction. There was a tendency for a negative correlation between cerebral activation in ipsilateral S1, M1 and PMC and the amplitude of motor evoked potentials in the tibialis anterior muscle elicited by transcranial magnetic stimulation, but this did not reach statistical significance. There was no correlation between motor score or spinal cord dimensions and the volume of the cortical motor areas. The observations show that lesion of descending tracts in the lateral part of the spinal cord results in increased activation in ipsilateral motor and sensory areas, which may help to compensate for the functional deficit following SCI.

Motivational Tuning of Fronto-Subthalamic Connectivity Facilitates Control of Action Impulses

It is critical for survival to quickly respond to environmental stimuli with the most appropriate action. This task becomes most challenging when response tendencies induced by relevant and irrelevant stimulus features are in conflict, and have to be resolved in real time. Inputs from the pre-supplementary motor area (pre-SMA) and inferior frontal gyrus (IFG) to the subthalamic nucleus (STN) are thought to support this function, but the connectivity and causality of these regions in calibrating motor control has not been delineated. In this study, we combined off-line noninvasive brain stimulation and functional magnetic resonance imaging, while young healthy human participants performed a modified version of the Simon task. We show that impairing pre-SMA function by noninvasive brain stimulation improved control over impulsive response tendencies, but only when participants were explicitly rewarded for fast and accurate responses. These effects were mediated by enhanced activation and connectivity of the IFG–STN pathway. These results provide causal evidence for a pivotal role of the IFG–STN pathway during action control. Additionally, they suggest a parallel rather than hierarchical organization of the pre-SMA–STN and IFG–STN pathways, since interruption of pre-SMA function can enhance IFG–STN connectivity and improve control over inappropriate responses.

Task-specific modulation of effective connectivity during two simple unimanual motor tasks: A 122-channel EEG study

Neural oscillations are thought to underlie coupling of spatially remote neurons and gating of information within the human sensorimotor system. Here we tested the hypothesis that different unimanual motor tasks are specifically associated with distinct patterns of oscillatory coupling in human sensorimotor cortical areas. In 13 healthy, right-handed subjects, we recorded task-induced neural activity with 122-channel electroencephalography (EEG) while subjects performed fast self-paced extension-flexion movements with the right index finger and an isometric contraction of the right forearm. Task-related modulations of inter-regional coupling within a core motor network comprising the left primary motor cortex (M1), lateral premotor cortex (lPM) and supplementary motor area (SMA) were then modeled using dynamic causal modeling (DCM). A network model postulating coupling both within and across frequencies best captured observed spectral responses according to Bayesian model selection. DCM revealed dominant coupling within the β-band (13-30 Hz) between M1 and SMA during isometric contraction of the forearm, whereas fast repetitive finger movements were characterized by strong coupling within the γ-band (31-48 Hz) and between the θ- (4-7 Hz) and the γ-band. This coupling pattern was mainly expressed in connections from lPM to SMA and from lPM to M1. We infer that human manual motor control involves task-specific modulation of inter-regional oscillatory coupling both within and across distinct frequency bands. The results highlight the potential of DCM to characterize context-specific changes in coupling within functional brain networks.

Action-blindsight in healthy subjects after transcranial magnetic stimulation

Clinical cases of blindsight have shown that visually guided movements can be accomplished without conscious visual perception. Here, we show that blindsight can be induced in healthy subjects by using transcranial magnetic stimulation over the visual cortex. Transcranial magnetic stimulation blocked the conscious perception of a visual stimulus, but subjects still corrected an ongoing reaching movement in response to the stimulus. The data show that correction of reaching movements does not require conscious perception of a visual target stimulus, even in healthy people. Our results support previous results suggesting that an efference copy is involved in movement correction, and this mechanism seems to be consistent even for movement correction without perception.

Abnormal dopaminergic modulation of striato-cortical networks underlies levodopa-induced dyskinesias in humans

Abnormal dopaminergic modulation of connectivity between the putamen and cortex is thought to underlie the emergence of levodopa-induced dyskinesias. Herz et al. confirm this directly by showing that in individuals with Parkinsons disease who have taken a single dose of levodopa, changes in connectivity preceding dyskinesias accurately predict their severity.