Cortical electrical stimulation, first performed by Bartholow in 1874, has become a gold standard method to explore various cortical functions and has greatly aided the field of functional neurosurgery to preserve eloquent cortices. Intracortical microstimulation techniques have evaluated orthodromic or antidromic responses in the remote cortical regions via cortico-cortical connections. Intracortical connections in humans have been studied almost exclusively by gross anatomic dissections. Direct cortical electrical stimulation has been shown to activate neurons in the motor cortex using not only conventional repetitive stimulation but also with single pulse stimulation. Direct cortical stimulation with single electric pulses through subdural electrodes elicited motor evoked potentials in awake patients with medically intractable partial epilepsy or multiple system atrophy. The present cortico-cortical evoked potentials studies revealed short and long cortico-cortical connections in vivo. Long cortico-cortical connections were observed by stimulating the lateral ventral or mesial prefrontal area.

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. Hum Brain Mapp, 2012. © 2011 Wiley Periodicals, Inc.

We analyzed volume and diffusivity measures of the corpus callosum (CC) in patients with temporal (TLE) and frontal (FLE) lobe epilepsy in comparison with healthy subjects. On high-resolution T1-weighted scans of 18 controls and 44 patients the volumes (cm(3)) of Witelson regions (WRs) and the entire CC were measured. The apparent diffusion coefficients (ADCs, 10(-5)mm(2)s(-1)) for the entire CC and three areas of interest were measured from co-registered ADC maps. The CC of patients with TLE and FLE, corrected for total brain volume, was smaller than that of controls. Patients' ADC values were higher than those of controls. Findings were significant for WR1, WR2, and WR6, the CC regions connecting the frontal and temporal lobes. Patients with FLE had smaller WR1 and higher ADC values; in patients with TLE, the findings were similar for WR6. Atrophy and increased diffusivity in subregions of the CC connecting homotopic contralateral cortical regions indicate anatomical abnormalities extending beyond the epileptogenic zone in FLE and TLE.

Purpose: Diffusion tensor imaging (DTI) provides information about magnitude (diffusivity) and directionality (anisotropy, FA) of water diffusion. We explored the characteristics of pathology-proven cortical dysplasia (CD) in the posterior quadrant in a case series of three patients using DTI measures, to assess associated alterations in subcortical connectivity and correlate with in situ epileptogenicity, seizure propagation and functional outcome.Methods: The FA maps were visually inspected by a Neuroradiologist blinded to clinical data and conventional MRI (PR) and tractography was performed to assess connectivity of the dysplastic cortex and correlate with seizure propagation on invasive EEG.Results: Analysis of FA maps revealed reduced connectivity with reduced arborization and thinning of the fiber bundles between the subcortical WM and the dysplastic cortex in patients 1 and 2, confirmed on tractography. Fiber tracts reconstructed from regions underlying the ictal onset help explain ictal propagation patterns. In the two patients without preexisting visual field deficit, resections spared the optic radiation visible on the FA map.Conclusions: Diffusivity measures and visualization of tracts provide complementary information on white matter changes accompanying CD and may assist to explain ictal spread patterns. Careful correlation with measures of function will allow the assessment of the functional significance of various dysplastic lesions and may help to design resective strategies. (C) 2010 Elsevier B.V. All rights reserved.

BACKGROUND:Dejerine and Benson and Geschwind postulated disconnection of the dominant angular gyrus from both visual association cortices as the basis for pure alexia, emphasizing disruption of white matter tracts in the dominant temporooccipital region. Recently functional imaging studies provide evidence for direct participation of basal temporal and occipital cortices in the cognitive process of reading. The exact location and function of these areas remain a matter of debate.OBJECTIVE:To confirm the participation of the basal temporal region in reading.METHOD:Extraoperative electrical stimulation of the dominant hemisphere was performed in three subjects using subdural electrodes, as part of presurgical evaluation for refractory epilepsy.RESULTS:Pure alexia was reproduced during cortical stimulation of the dominant posterior fusiform and inferior temporal gyri in all three patients. Stimulation resulted in selective reading difficulty with intact auditory comprehension and writing. Reading difficulty involved sentences and words with intact letter by letter reading. Picture naming difficulties were also noted at some electrodes. This region is located posterior to and contiguous with the basal temporal language area (BTLA) where stimulation resulted in global language dysfunction in visual and auditory realms. The location corresponded with the visual word form area described on functional MRI.CONCLUSION:These observations support the existence of a visual language area in the dominant fusiform and occipitotemporal gyri, contiguous with basal temporal language area. A portion of visual language area was exclusively involved in lexical processing while the other part of this region processed both lexical and nonlexical symbols.

BACKGROUND:A subgroup of patients with nonlesional temporal lobe epilepsy (TLE) has no evidence of hippocampal sclerosis on standard temporal lobe protocol MRI.OBJECTIVE:To investigate whether interictal diffusion-weighted imaging adds lateralizing information in patients with TLE with and without lateralizing conventional MRI.METHODS:We studied 22 patients (9 right, 13 left TLE) who had undergone temporal lobectomy and 18 control subjects. We measured hippocampal volumes on high- resolution coronal magnetization-prepared rapid gradient echo scans. Apparent diffusion coefficients (ADCs) for the entire hippocampus and three arbitrarily defined areas of interest within the hippocampal head, body, and tail were measured from the coregistered ADC map. Pathology was reviewed and correlated with imaging findings.RESULTS:Fourteen of 22 patients had hippocampal atrophy on MRI (defined as volume asymmetry greater than 2 SDs compared with asymmetry in the control group). Overall, resected hippocampi (n = 22) were significantly smaller than contralateral hippocampi as well as ipsilateral hippocampi in controls. ADCs were significantly higher in resected hippocampi than contralateral hippocampi as well as ipsilateral hippocampi in controls. These differences were also observed within the three areas of interest. ADCs in the hippocampi contralateral to the epileptogenic zone (n = 22) were also higher than in ipsilateral hippocampi in controls. In the subgroup of eight patients with nonlateralizing conventional MRIs, ADCs of resected hippocampi were not significantly different compared with the contralateral side. Pathology in these patients revealed gliosis only without apparent neuron loss.CONCLUSION:Interictal apparent diffusion coefficients confirm lateralization in patients with hippocampal atrophy on standard temporal lobe protocol MRI. However, they do not provide lateralizing information in patients with nonlateralizing conventional MRI.

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.

OBJECTNeuroendoscopic 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.METHODSTo 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.CONCLUSIONSThis 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.

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.