Parieto-frontal network in humans studied by cortico-cortical evoked potential.

Parieto-frontal network is essential for sensorimotor integration in various complex behaviors, and its disruption is associated with pathophysiology of apraxia and visuo-spatial disorders. Despite advances in knowledge regarding specialized cortical areas for various sensorimotor transformations, little is known about the underlying cortico-cortical connectivity in humans. We investigated inter-areal connections of the lateral parieto-frontal network in vivo by means of cortico-cortical evoked potentials (CCEPs). Six patients with epilepsy and one with brain tumor were studied. With the use of subdural electrodes implanted for presurgical evaluation, network configuration was investigated by tracking the connections from the parietal stimulus site to the frontal site where the maximum CCEP was recorded. It was characterized by (i) a near-to-near and distant-to-distant, mirror symmetric configuration across the central sulcus, (ii) preserved dorso-ventral organization (the inferior parietal lobule to the ventral premotor area and the superior parietal lobule to the dorsal premotor area), and (iii) projections to more than one frontal cortical sites in 56% of explored connections. These findings were also confirmed by the standardized parieto-frontal CCEP connectivity map constructed in reference to the Jülich cytoarchitectonic atlas in the MNI standard space. The present CCEP study provided an anatomical blueprint underlying the lateral parieto-frontal network and demonstrated a connectivity pattern similar to non-human primates in the newly developed inferior parietal lobule in humans.

Cortical stimulation for language mapping in focal epilepsy: correlations with tractography of the arcuate fasciculus.

PURPOSE: Diffusion tensor imaging (DTI) provides information about magnitude (diffusivity) and directionality (fractional anisotropy, FA) of water diffusion and allows visualization of major white matter tracts. The arcuate fasciculus (AF) connects anterior (Broca's) and posterior (Wernicke's) language areas. We hypothesized that essential language areas identified by direct cortical stimulation would colocalize with areas revealing subcortical connectivity via the AF. METHODS: Fourteen patients with pharmacoresistant left hemispheric epilepsy and left hemisphere language dominance underwent invasive evaluations for localization of epileptogenicity and functional mapping. DTI and T1-weighted volumetric magnetic resonance imaging (MRI) scans were coregistered, and subdural grid electrodes identified on postimplantation computed tomography (CT) scans were also coregistered to the MRI scans. The AF was reconstructed from a region lateral to the corona radiata on the FA map. Colocalization, defined as <1 cm between the AF and the electrode positions delineating language cortex, was visually assessed with excellent reliability (Cronbach's alpha = 0.98). RESULTS: A total of 71 subdural grid contacts were overlying language cortex. Nineteen contacts in eight patients were over Broca's area, 16 of which (84.2%) colocalized with the AF. Fifty-two contacts in 10 patients were over Wernicke's area, with colocalization in 29 patients (55.8%). Colocalization was significantly greater in anterior regions than in posterior regions [chi(2)(1) = 4.850, p < 0.05]. DISCUSSION: The AF, as visualized with DTI, colocalized well with anterior language areas, but less so with posterior language areas, inferring that the latter are more spatially dispersed.

Functional connectivity in human cortical motor system: a cortico-cortical evoked potential study.

In order to understand the complex functional organization of the motor system, it is essential to know the anatomical and functional connectivity among individual motor areas. Clinically, knowledge of these cortico-cortical connections is important to understand the rapid spread of epileptic discharges through the network underlying ictal motor manifestation. In humans, however, knowledge of neuronal in vivo connectivity has been limited. We recently reported a new method, 'cortico-cortical evoked potential (CCEP)', to electrically track the cortico-cortical connections by stimulating a part of the brain through subdural electrodes and recording the cortical evoked potentials that emanate from a distant region of the cortex via neuronal projections. We applied the CCEP methodology to investigate in vivo cortico-cortical connections between the lateral motor cortex [LMCx; sensorimotor (SM) and lateral premotor areas] and the medial motor cortex [MMCx; supplementary motor area proper (SMA), pre-SMA and foot SM]. Seven patients with intractable partial epilepsy were studied. These patients had chronic implantation of subdural electrodes covering part of the lateral and medial frontal areas. As a part of the routine pre-surgical evaluation, comprehensive cortical mapping was performed by electrical stimulation of the subdural electrodes, and the precise localization of the subdural electrodes was defined by MRI co-registration. Single-pulse electrical stimuli were delivered to MMCx (7 patients) and LMCx (4), and CCEPs time-locked to the stimuli were recorded by averaging electrocorticograms from LMCx and MMCx, respectively. Short-latency CCEPs were observed when stimulating MMCx and recording from LMCx (mean latency: 21.6 ms, range: 9-47 ms) and vice versa when stimulating LMCx and recording from MMCx (mean latency: 29.4 ms, range: 11-57 ms). In terms of the location of these stimulus sites and CCEP responses along the rostrocaudal axis, regression analysis revealed a consistent correlation between the sites of stimulation and maximum CCEP for stimulation of both MMCx and LMCx. Functionally, stimulation of the positive motor areas in MMCx elicited CCEPs at the somatotopically homologous regions in LMCx (71%). The same findings were observed in MMCx (82%) upon stimulation of LMCx. In four subjects in whom bi-directional connectivity was investigated by stimulating both MMCx and LMCx, reciprocality was observed in the majority of connections (78-94%). In conclusion, the present study demonstrated a human motor cortico-cortical network connecting (i) anatomically homologous areas of LMCx and MMCx along the rostrocaudal cognitive-motor gradient; and (ii) somatotopically homologous regions in LMCx and MMCx in a reciprocal manner.

Functional connectivity in the human language system: a cortico-cortical evoked potential study.

A better understanding of the mechanisms involved in human higher cortical functions requires a detailed knowledge of neuronal connectivity between functional cortical regions. Currently no good method for tracking in vivo neuronal connectivity exists. We investigated the inter-areal connections in vivo in the human language system using a new method, which we termed 'cortico-cortical evoked potentials' (CCEPs). Eight patients with epilepsy (age 13-42 years) underwent invasive monitoring with subdural electrodes for epilepsy surgery. Six patients had language dominance on the side of grid implantation and two had bilateral language representation by the intracarotid amobarbital test. Conventional cortical electrical stimulation was performed to identify the anterior and posterior language areas. Single pulse electrical stimuli were delivered to the anterior language (eight patients), posterior language (four patients) or face motor (two patients) area, and CCEPs were obtained by averaging electrocorticograms (ECoGs) recorded from the perisylvian and extrasylvian basal temporal language areas time-locked to the stimulus. The subjects were not asked to perform any tasks during the study. Stimulation at the anterior language area elicited CCEPs in the lateral temporo-parietal area (seven of eight patients) in the middle and posterior part of the superior temporal gyrus, the adjacent part of the middle temporal gyrus and the supramarginal gyrus. CCEPs were recorded in 3-21 electrodes per patient. CCEPs occurred at or around the particular electrodes in the posterior language area which, when stimulated, produced speech arrest. Similar early and late CCEPs were obtained from the basal temporal area by stimulating the anterior language area (three of three patients). In contrast, stimulation of the adjacent face motor area did not elicit CCEPs in language areas but rather in the postcentral gyrus. Stimulation of the posterior language area produced CCEPs in the anterior language (three of four patients) as well as in the basal temporal area (one of two patients). These CCEPs were less well defined. These findings suggest that perisylvian and extrasylvian language areas participate in the language system as components of a network by means of feed-forward and feed-back projections. Different from the classical Wernicke-Geschwind model, the present study revealed a bidirectional connection between Broca's and Wernicke's areas probably through the arcuate fasciculus and/or the cortico-subcortico-cortical pathway. CCEPs were recorded from a larger area than the posterior language area identified by electrical stimulation. This suggests the existence of a rather broad neuronal network surrounding the previously recognized core region of this area.

Image-guided endoscopy: description of technique and potential applications.

OBJECT: Neuroendoscopic approaches to lesions of the central nervous system and spine are limited by the loss of stereoscopic vision and high-fidelity image quality inherent in the operating microscope. Image-guided endoscopy (IGE) and image-guided surgery (IGS) have the potential to overcome these limitations. The goal of this study was to evaluate IGE for its potential applications in neurosurgery. METHODS: To determine the feasibility of IGE, a rigid endoscope was tracked using an IGS system that provided navigational data for the endoscope tip and trajectory as well as a computer-generated, three-dimensional, virtual representation of the image provided by the endoscope. The IGE procedure was successfully completed in 14 patients (nine with pituitary adenomas, one with a temporal cavernous malformation, and four with unruptured aneurysms). No complications could be attributed to the procedure. Compared with direct microscopy performed using anatomical landmarks, registration of the endoscope, and virtual image were highly accurate. CONCLUSIONS: This procedure offers many potential advantages for central nervous system and spinal endoscopy. Advances in IGE may enable its application to regions outside the central nervous system as well.

The mind's eye: functional MR imaging evaluation of golf motor imagery.

BACKGROUND AND PURPOSE: Mental imagery involves rehearsing or practicing a task in the mind with no physical movement. The technique is commonly used, but the actual physical foundation of imagery has not been evaluated for the fast, complex, automatic motor movement of the golf swing. This study evaluated motor imagery of the golf swing, of golfers of various handicaps, by using functional MR imaging to assess whether areas of brain activation could be defined by this technique and to define any association between activated brain areas and golf skill. METHODS: Six golfers of various handicap levels were evaluated with functional MR imaging during a control condition and during mental imagery of their golf swing. Two control conditions were evaluated--"rest" and "wall"--and were then subtracted from the experimental condition to give the functional activation map. These control conditions were then tested against the golf imagery; the participants were told to mentally rehearse their golf swings from a first person perspective. The percentages of activated pixels in 137 defined regions of interest were calculated. RESULTS: The "rest-versus-golf" paradigm showed activation in motor cortex, parietal cortex, frontal lobe, cerebellum, vermis, and action planning areas (frontal and parietal cortices, supplementary motor area, cerebellum) and areas involved with error detection (cerebellum). Vermis, supplementary motor area, cerebellum, and motor regions generally showed the greatest activation. Little activation was seen in the cingulate gyrus, right temporal lobe, deep gray matter, and brain stem. A correlation existed between increased number of areas of activation and increased handicap. CONCLUSION: This study showed the feasibility of defining areas of brain activation during imagery of a complex, coordinated motor task. Decreased brain activation occurred with increased golf skill level for the supplementary motor area and cerebellum with little activation of basal ganglia.

Recovery of pain control by intensive reprogramming after loss of benefit from motor cortex stimulation for neuropathic pain.

INTRODUCTION: Motor cortex stimulation (MCS) may serve as an adjunct in managing neuropathic pain after other conservative and interventional methods have failed. However, the magnitude and duration of the benefit are highly variable, with a significant percentage of patients losing pain relief over time. We investigated whether intensive reprogramming could recapture the beneficial effects of MCS. METHODS: Six patients who had previously undergone MCS implantation for neuropathic pain but had lost benefit were brought back for 1-5 days of intensive reprogramming. Four patients were evaluated as inpatients while the others were seen as outpatients during multiple visits over several days. Several hours a day were spent with each patient. Patients completed visual analog scale (VAS) ratings at intervals throughout the reprogramming period to judge effectiveness of stimulation. Pre- and postadjustment VAS were compared using a paired t test. RESULTS: The patients' average age was 50 years (range 26-71). The diagnoses were trigeminal neuropathic pain (2 patients), complex regional pain syndrome I (2), phantom limb pain (1) and poststroke pain (1). The mean duration of pain was 6 years. The MCS benefit had initially lasted for a mean of 7.16 months (range 2-18 months). After reprogramming, 5 of 6 patients experienced improvement in pain. Average VAS scores decreased from 7.44 to 2.28 (p < 0.001) in those patients who responded to reprogramming. The average stimulation parameters in these patients were 5 V amplitude (range 1.7-10), 313 micros pulse width (range 240-390) and frequency of 84 Hz (range 55-130). Three patients experienced seizures during reprogramming. The mean seizure threshold was 8.9 V. No patient experienced seizures at their therapeutic settings. Pain control has been maintained after discharge. CONCLUSION: Intensive reprogramming can recapture the benefit of MCS in patients who have lost pain control. The use of broad dipoles using two contacts rather than one contact of the 1 x 4 electrode array improved the ability to recapture beneficial stimulation. There is a significant risk of seizures during aggressive reprogramming.

Neocortical temporal FDG-PET hypometabolism correlates with temporal lobe atrophy in hippocampal sclerosis associated with microscopic cortical dysplasia.

PURPOSE: Medically intractable temporal lobe epilepsy (TLE) due to hippocampal sclerosis (HS), with or without cortical dysplasia (CD), is associated with atrophy of the hippocampal formation and regional fluorodeoxyglucose positron-emission tomography (FDG-PET) hypometabolism. The relation between areas of functional and structural abnormalities is not well understood. We investigate the relation between FDG-PET metabolism and temporal lobe (TL) and hippocampal atrophy in patients with histologically proven isolated HS and HS associated with CD. METHODS: Twenty-three patients underwent en bloc resection of the mesial and anterolateral neocortical structures. Ten patients were diagnosed with isolated HS; 13 patients had associated microscopic CD. Temporal lobe volumes (TLVs) and hippocampal volumes were measured. Magnetic resonance imaging (MRI) and PET were co-registered, and regions of interest (ROIs) determined as gray matter of the mesial, lateral, and anterior temporal lobe. RESULTS: All patients (HS with or without CD) had significant ipsilateral PET hypometabolism in all three regions studied (p < 0.0001). In patients with isolated HS, the most prominent hypometabolism was in the anterior and mesial temporal lobe, whereas in dual pathology, it was in the lateral temporal lobe. TLVs and hippocampal volumes were significantly smaller on the epileptogenic side (p < 0.05). The PET asymmetries ipsilateral/contralateral to the epileptogenic zone and TLV asymmetries correlated significantly for the anterior and lateral temporal lobes (p < 0.05) in the HS+CD group, but not in the isolated HS group. Mesial temporal hypometabolism was not significantly different between the two groups. CONCLUSIONS: Temporal neocortical microscopic CD with concurrent HS is associated with more prominent lateral temporal metabolic dysfunction compared with isolated HS in TL atrophy. Further studies are needed to confirm these findings and correlate the PET hypometabolic patterns with outcome data in patients operated on for HS with or without CD.

Epileptogenicity of focal malformations due to abnormal cortical development: direct electrocorticographic-histopathologic correlations.

PURPOSE: Malformations due to abnormal cortical development (MCDs) are common pathologic substrates of medically intractable epilepsy. The in situ epileptogenicity of these lesions as well as its relation to histopathologic changes remains unknown. The purpose of this study was to correlate the cellular patterns of MCDs with the expression of focal cortical epileptogenicity as assessed by direct extraoperative electrocorticographic (ECoG) recordings by using subdural grids. METHODS: Fifteen patients with drug-resistant focal epilepsy due to pathologically confirmed MCD who underwent subdural electrode placement for extraoperative seizure localization and cortical mapping between 1997 and 2000 were included in the study. Areas of interictal spiking and ictal-onset patterns were identified and separated during surgery for further pathologic characterization (cellular and architectural). Three pathologic groups were identified: type I; architectural disorganization with/without giant neurons, type IIA; architectural disorganization with dysmorphic neurons, and type IIB; architectural disorganization, dysmorphic neurons, and balloon cells (BCs). The focal histopathologic subtypes of MCDs in cortical tissue resected were then retrospectively correlated with in situ extraoperative ECoG patterns. RESULTS: Cortical areas with histopathologic subtype IIA showed significantly higher numbers of slow repetitive spike pattern in comparison with histopathologic type I (p = 0.007) and normal pathology (p = 0.002). The ictal onset came mainly from cortical areas with histopathologic type IIA (nine of 15 patients). None of the seizures originated from neocortical areas that showed BC-containing MCD (type IIB). CONCLUSIONS: This study shows that areas containing BCs are less epileptogenic than are closely located dysplastic regions. These results suggest a possible protective effect of BCs or a severe disruption in the neuronal networks in BCs containing dysplastic lesions. Further studies are needed to elucidate the nature and the potential role(s) of balloon cells in MCD-induced epileptogenicity.