Tuomas Neuvonen

Preoperative Functional Mapping for Rolandic Brain Tumor Surgery: Comparison of Navigated Transcranial Magnetic Stimulation to Direct Cortical Stimulation

BACKGROUND:Transcranial magnetic stimulation (TMS) is the only noninvasive method for presurgical stimulation mapping of cortical function. Recent technical advancements have significantly increased the focality and usability of the method. OBJECTIVE:To compare the accuracy of a 3-dimensional magnetic resonance imaging-navigated TMS system (nTMS) with the gold standard of direct cortical stimulation (DCS). METHODS:The primary motor areas of 20 patients with rolandic tumors were mapped preoperatively with nTMS at 110% of the individual resting motor threshold. Intraoperative DCS was available from 17 patients. The stimulus locations eliciting the largest electromyographic response in the target muscles (“hotspots”) were determined for both methods. RESULTS:The nTMS and DCS hotspots were located on the same gyrus in all cases. The mean ± SEM distance between the nTMS and DCS hotspots was 7.83 ± 1.18 mm for the abductor pollicis brevis (APB) muscle (n = 15) and 7.07 ± 0.88 mm for the tibialis anterior muscle (n = 8). When a low number of DCS stimulations was performed, the distance between the nTMS and DCS hotspots increased substantially (r = −0.86 for APB). After the exclusion of the cases with < 15 DCS APB responses, the mean ± SEM distance between the hotspots was only 4.70 ± 1.09 mm for APB (n = 8). CONCLUSION:Peritumoral mapping of the motor cortex by nTMS agreed well with the gold standard of DCS. Thus, nTMS is a reliable tool for preoperative mapping of motor function.

Cognitive and motor loops of the human cerebro-cerebellar system

We applied fMRI and diffusion-weighted MRI to study the segregation of cognitive and motor functions in the human cerebro-cerebellar system. Our fMRI results show that a load increase in a nonverbal auditory working memory task is associated with enhanced brain activity in the parietal, dorsal premotor, and lateral prefrontal cortices and in lobules VII–VIII of the posterior cerebellum, whereas a sensory-motor control task activated the motor/somatosensory, medial prefrontal, and posterior cingulate cortices and lobules V/VI of the anterior cerebellum. The load-dependent activity in the crus I/II had a specific relationship with cognitive performance: This activity correlated negatively with load-dependent increase in RTs. This correlation between brain activity and RTs was not observed in the sensory-motor task in the activated cerebellar regions. Furthermore, probabilistic tractography analysis of the diffusion-weighted MRI data suggests that the tracts between the cerebral and the cerebellar areas exhibiting cognitive load-dependent and sensory-motor activity are mainly projected via separated pontine (feed-forward tracts) and thalamic (feedback tracts) nuclei. The tractography results also indicate that the crus I/II in the posterior cerebellum is linked with the lateral prefrontal areas activated by cognitive load increase, whereas the anterior cerebellar lobe is not. The current results support the view that cognitive and motor functions are segregated in the cerebellum. On the basis of these results and theories of the function of the cerebellum, we suggest that the posterior cerebellar activity during a demanding cognitive task is involved with optimization of the response speed.

Major depressive disorder and white matter abnormalities: A diffusion tensor imaging study with tract-based spatial statistics

BACKGROUND A few diffusion tensor imaging (DTI) studies have shown abnormalities in areas of white matter tracts involved in mood regulation in geriatric depressive patients, using a region-of-interest technique. A voxel-based morphometry DTI study of young depressive patients reported similar results. In this study, we explored the structure of the white matter of the whole brain with DTI in middle-aged major depressive disorder (MDD) patients, using novel tract-based spatial statistics. METHODS Sixteen MDD patients and 20 controls underwent DTI. An automated tract-based spatial method (TBSS) was used to analyze the scans. RESULTS Compared with controls, the MDD patients showed a trend for lower values of fractional anisotropy (FA) in the left sagittal stratum, and suggestive decreased FA in the right cingulate cortex and posterior body of corpus callosum. Regressing out the duration and severity of disorder in the model did not change the finding in the sagittal stratum, but dissipated the decrease of FA in latter regions. LIMITATIONS Possibly by reason of a relatively small study sample for a TBSS, the results are suggestive, and should be replicated in further studies. CONCLUSIONS A novel observer-independent DTI method showed decreased FA in the middle-aged MDD patients in white matter regions that have previously connected to the emotional regulation. Lower FA might imply underlying structural abnormalities that contribute to the dysfunction detected in the limbic-cortical network of depressive patients.

Effects of an NMDA-receptor antagonist MK-801 on an MMN-like response recorded in anesthetized rats.

In the human brain, auditory sensory memory has been extensively studied using a well-defined component of event-related potential named the mismatch negativity (MMN). The MMN is generated in the auditory and frontal cortices in response to deviant stimuli. In monkeys, cortical N-methyl-d-aspartate (NMDA) receptors have a central role in the generation of the MMN. MMN-like responses have also been recorded in other animals, including rats. The present study aimed at determining whether the MMN-like response in rats depends on an intact NMDA-receptor system. We recorded auditory evoked responses during an oddball paradigm epidurally in anesthetized rats that had received intraperitoneal injections of saline or an NMDA-receptor antagonist MK-801. An MMN-like response was recorded in the oddball paradigm in saline-treated rats. Further, this response was dose-dependently blocked by MK-801. These results suggest that the MMN-like response in rats depends on an intact NMDA-receptor system.

A novel approach for documenting naming errors induced by navigated transcranial magnetic stimulation

Transcranial magnetic stimulation (TMS) is widely used both in basic research and in clinical practice. TMS has been utilized in studies of functional organization of speech in healthy volunteers. Navigated TMS (nTMS) allows preoperative mapping of the motor cortex for surgical planning. Recording behavioral responses to nTMS in the speech-related cortical network in a manner that allows off-line review of performance might increase utility of nTMS both for scientific and clinical purposes, e.g., for a careful preoperative planning. Four subjects participated in the study. The subjects named pictures of objects presented every 2-3s on a computer screen. One-second trains of 5 pulses were applied by nTMS 300ms after the presentation of pictures. The nTMS and stimulus presentation screens were cloned. A commercial digital camera was utilized to record the subjects performance and the screen clones. Delays between presentation, audio and video signals were eliminated by carefully tested combination of displays and camera. An experienced neuropsychologist studied the videos and classified the errors evoked by nTMS during the object naming. Complete anomias, semantic, phonological and performance errors were observed during nTMS of left fronto-parieto-temporal cortical regions. Several errors were detected only in the video classification. nTMS combined with synchronized video recording provides an accurate monitoring tool of behavioral TMS experiments. This experimental setup can be particularly useful for high-quality cognitive paradigms and for clinical purposes.

Dose-related effects of memantine on a mismatch negativity-like response in anesthetized rats

Memantine is a low-affinity NMDA receptor antagonist that is used in the treatment of Alzheimers disease to alleviate the cognitive symptoms of the disease. In humans, memantine has been shown to facilitate auditory change detection as reflected in the mismatch negativity (MMN) response recorded in the frontal cortex. In the present study we investigated the effects of memantine on the auditory MMN-like responses recorded in anesthetized rats. Saline, a low (3 mg/kg) or a high (10 mg/kg) dose of memantine was i.p. injected into the animals. Auditory MMN-like responses were recorded during the presentation of a repeated tone of one frequency (standard, P=0.956) that was rarely replaced by a tone of another frequency (deviant, P=0.044). The low dose of memantine did not observably affect the amplitude of the auditory MMN-like response, but it prolonged the duration of the response relative to saline. The high dose of memantine, in contrast, blocked the generation of the auditory MMN-like response. The findings suggest that memantine may, with appropriate doses, facilitate already this early stage of auditory processing.

Increasing top-down suppression from prefrontal cortex facilitates tactile working memory

Navigated transcranial magnetic stimulation (TMS) combined with diffusion-weighted magnetic resonance imaging (DW-MRI) and tractography allows investigating functional anatomy of the human brain with high precision. Here we demonstrate that working memory (WM) processing of tactile temporal information is facilitated by delivering a single TMS pulse to the middle frontal gyrus (MFG) during memory maintenance. Facilitation was obtained only with a TMS pulse applied to a location of the MFG with anatomical connectivity to the primary somatosensory cortex (S1). TMS improved tactile WM also when distractive tactile stimuli interfered with memory maintenance. Moreover, TMS to the same MFG site attenuated somatosensory evoked responses (SEPs). The results suggest that the TMS-induced memory improvement is explained by increased top-down suppression of interfering sensory processing in S1 via the MFG-S1 link. These results demonstrate an anatomical and functional network that is involved in maintenance of tactile temporal WM.

Modeling anisotropic light propagation in a realistic model of the human head

A Monte Carlo model capable of describing photon migration in arbitrary three-dimensional geometry with spatially varying optical properties and tissue anisotropy is presented. We use the model to explore the effects of anisotropy for optical measurements of the human head. An anisotropic diffusion equation that corresponds to our Monte Carlo model is derived, and a comparison between the Monte Carlo model and the diffusion equation solution with finite elements is given.

Navigated transcranial magnetic stimulation of the primary somatosensory cortex impairs perceptual processing of tactile temporal discrimination

Previous studies indicate that transcranial magnetic stimulation (TMS) with biphasic pulses applied approximately over the primary somatosensory cortex (S1) suppresses performance in vibrotactile temporal discrimination tasks; these previous results, however, do not allow separating perceptual influence from memory or decision-making. Moreover, earlier studies using external landmarks for directing biphasic TMS pulses to the cortex do not reveal whether the changes in vibrotactile task performance were due to action on S1 or an adjacent area. In the present study, we determined whether the S1 area representing a cutaneous test site is critical for perceptual processing of tactile temporal discrimination. Electrical test pulses were applied to the thenar skin of the hand and the subjects attempted to discriminate single from twin pulses. During discrimination task, monophasic TMS pulses or sham TMS pulses were directed anatomically accurately to the S1 area representing the thenar using magnetic resonance image-guided navigation. The subjects capacity to temporal discrimination was impaired with a decrease in the delay between the TMS pulse and the cutaneous test pulse from 50 to 0 ms. The result indicates that S1 area representing a cutaneous test site is involved in perceptual processing of tactile temporal discrimination.

Distracters Impair and Create Working Memory–Related Neuronal Activity in the Prefrontal Cortex

The prefrontal cortex (PFC) has a central role in working memory (WM). Resistance to distraction is considered a fundamental feature of WM and PFC neuronal activity. However, although unexpected stimuli often disrupt our work, little is known about the underlying neuronal mechanisms involved. In the present study, we investigated whether irregularly presented distracters disrupt WM task performance and underlying neuronal activity. We recorded single neuron activity in the PFC of 2 monkeys performing WM tasks and investigated effects of auditory and visual distracters on WM performance and neuronal activity. Distracters impaired memory task performance and affected PFC neuronal activity. Distraction that was of the same sensory modality as the memorandum was more likely to impair WM performance and interfere with memory-related neuronal activity than information that was of a different sensory modality. The study also shows that neurons not involved in memory processing in less demanding conditions may become engaged in WM processing in more demanding conditions. The study demonstrates that WM performance and underlying neuronal activity are vulnerable to irregular distracters and suggests that the PFC has mechanisms that help to compensate for disruptive effects of external distracters.