Personal recovery associated with deep brain stimulation for treatment-resistant depression: A constructivist grounded theory study.

WHAT IS KNOWN ON THE SUBJECT?: Major depressive disorder is the most prevalent of all mental illnesses. 10%-20% of patients with depression and 1% of the population overall have treatment-resistant depression (TRD). DBS is an emerging investigational treatment for TRD with documented clinical efficacy and safety. The framework of the recovery model includes both clinical and personal recovery. Personal recovery is a self-process in which hope, empowerment and optimism are embraced to overcome the impact of mental illness on one's sense of self. Although clinical and functional outcomes of DBS for TRD have been well documented in the previous studies, personal recovery as an outcome has been explored only in a handful of studies. WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE?: This is the first qualitative study exploring personal recovery from DBS treatment specific to the target of subcallosal cingulate cortex in patients with TRD. Since the existing literature on personal recovery in DBS studies is limited, the contribution of this paper is crucial to this field. For individuals who responded to deep brain stimulation clinically, neither participants nor family believed it cured their depression, but rather there was a significant decrease in the severity of symptoms of depression. A holistic-oriented framework (that includes personal recovery) is significant for those individuals with TRD undergoing DBS. Personal and clinical recovery are two different constructs, and individuals may experience one or the other or both. The experience of participants who responded to deep brain stimulation recognized that the recovery from depression is a process of reconstructing self. This process involved a period of adjustment that evoked a deeper self-awareness, re-engagement with daily living and newfound gratitude in living. Individuals transitioned from an emotionally driven life to one where future goals were considered. Supportive relationships were instrumental in this process. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: A deep brain stimulation intervention for treatment-resistant depression offered individuals an opportunity for personal recovery where a reconstruction of self occurred. Personal recovery can be considered as an outcome in conjunction with clinical and functional outcomes in future DBS trials for TRD. The relevance of personal recovery in the prevention of relapses needs further investigation. To advocate for care and services that facilitate the process of recovery from depression, it is important to understand the personal dimensions and experience of recovery that may influence the process. To develop recovery-oriented interventions to help patients and families in recovery post-deep brain stimulation, further understanding of support and negotiating relationships during this life-altering experience is needed. ABSTRACT: Introduction Multiple trials of antidepressant treatments in patients with depression pose a major challenge to the mental health system. Deep brain stimulation (DBS) is an emerging and promising investigational treatment to reduce depressive symptoms in individuals with treatment-resistant depression (TRD). The clinical and functional outcomes of DBS for TRD have been well documented in previous studies; however, studies of personal recovery as an outcome of DBS specific to the target of subcallosal cingulate cortex in patients with TRD are limited. Aim To explore the processes of personal recovery in patients with treatment-resistant depression following subcallosal cingulate-deep brain stimulation. Method Participants were 18 patients with TRD who participated in the subcallosal cingulate (SCC)-DBS trial and 11 family members. They also participated in add-on individual cognitive behavioural therapy during the trial. A qualitative constructivist grounded theory approach was used to conceptualize the personal recovery process of patients and families. Results While every participant and their families' journey were unique following the deep brain stimulation intervention, a theoretical model of Balancing to Establish a Reconstructed Self emerged from the data. The themes underlying the model were (1) Balancing to Establish a Reconstructed Self: A Whole-Body Experience, (2) The Liminal Space in-between: Balancing with Cautious Optimism, (3) Hope: Transitioning from Emotion-Focussed Living to Goal-Oriented Planning and (4) Support: Negotiating Relationships. Discussion This is the first study examining recovery from patients' perspectives as an outcome of SCC-DBS intervention for TRD. The study shows that personal recovery is a gradual and continual process of reconstruction of the self, developing through supportive relationships. Clinical and personal recovery are two distinct constructs, and individuals may experience one or the other or both. Most patients who do respond clinically experience improvement in terms of having optimism and hope. Some patients, however, respond with significant symptom reduction but are not able to achieve personal recovery to experience joy or hope for improved quality of living. Implications for Practice Strategies for personal recovery for both patients and family need to be considered during and post deep brain stimulation intervention. Nurses working with these patients and families may benefit from education, training and support to assess and engage in conversations about their recovery process.

Limb Preference Changes after Focused-Ultrasound Thalamotomy for Tremor.

BACKGROUND: Magnetic resonance-guided focused-ultrasound (MRgFUS) thalamotomy is an effective treatment for essential and other tremors. It targets the ventrointermedius (Vim) nucleus, which is the thalamic relay in a proprioceptive pathway, and contains kinesthetic cells. Although MRgFUS thalamotomy reduces some risks associated with more invasive surgeries, it still has side effects, such as balance and gait disturbances; these may be caused by the lesion impacting proprioception. OBJECTIVES: Our aim was to quantitatively measure the effects of MRgFUS on proprioception and limb use in essential tremor patients. We hypothesized that this thalamotomy alters proprioception, because the sensorimotor Vim thalamus is lesioned. METHODS: Proprioception was measured using the Kinarm exoskeleton robot in 18 patients. Data were collected pre-operatively, and then 1 day, 3 months, and 1 year after surgery. Patients completed four tasks, assessing motor coordination and postural control, goal-directed movement and bimanual planning, position sense, and kinesthesia. RESULTS: Immediately after surgery there were changes in posture speed (indicating tremor improvement), and in bimanual hand use, with the untreated limb being preferred. However, these measures returned to pre-operative baseline over time. There were no changes in parameters related to proprioception. None of these measures correlated with lesion size or lesion-overlap with the dentato-rubro-thalamic tract. CONCLUSIONS: This is the first quantitative assessment of proprioception and limb preference following MRgFUS thalamotomy. Our results suggest that focused-ultrasound lesioning of the Vim thalamus does not degrade proprioception but alters limb preference. This change may indicate a required "relearning" in the treated limb, because the effect is transient. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Outcomes of Occipital Nerve Stimulation for Craniofacial Pain Syndromes.

OBJECTIVES: Occipital nerve regional stimulation (ONS) is reported to improve pain in several studies. We examined long-term pain and functional outcomes of ONS in an open-label prospective study. METHODS: Patients with medically refractory and disabling craniofacial pain were prospectively selected for ONS. Primary outcome was a change in mean daily pain intensity on the numeric pain rating scale (NPRS) at 6 months. Secondary outcomes included changes in NPRS, Headache Impact Test-6 (HIT-6), Migraine Disability Assessment (MIDAS), Pain Disability Index (PDI), Center for Epidemiologic Studies Depression Scale - Revised (CESD-R), and Short Form-36 version 2 (SF36) at last follow-up. RESULTS: Thirteen patients (mean age 49.7 ± 8.4) diagnosed with occipital neuralgia (6), hemicrania continua (2), persistent idiopathic facial pain (2), post-traumatic facial pain (1), cluster headache (1), and chronic migraine (1) were enrolled. Mean NPRS improved by 2.1 ± 2.1 at 6 months and 2.1 ± 1.9 at last follow-up (23.5 ± 18.1 months). HIT-6 decreased by 8.7 ± 8.8, MIDAS decreased by 61.3 ± 71.6, and PDI decreased by 17.9 ± 18. SF36 physical functioning, bodily pain, and social functioning improved by 16.4 ± 19.6, 18.0 ± 31.6, and 26.1 ± 37.3, respectively. Moderate to severe headache days (defined as ≥50% of baseline mean NPRS) were reduced by 8.9 ± 10.2 days per month with ONS. CONCLUSION: ONS reduced the long-term NPRS and moderate-severe monthly headache days by 30% and improved functional outcomes and quality of life. A prospective registry for ONS would be helpful in accumulating a larger cohort with longer follow-up in order to improve the use of ONS.

Neurovascular coupling during deep brain stimulation.

BACKGROUND: Deep brain stimulation (DBS) is an effective treatment for movement disorders, yet its mechanisms of action remain unclear. One method used to study its circuit-wide neuromodulatory effects is functional magnetic resonance imaging (fMRI) which measures hemodynamics as a proxy of neural activity. To interpret functional imaging data, we must understand the relationship between neural and vascular responses, which has never been studied with the high frequencies used for DBS. OBJECTIVE: To measure neurovascular coupling in the rat motor cortex during thalamic DBS. METHOD: Simultaneous intrinsic optical imaging and extracellular electrophysiology was performed in the motor cortex of urethane-anesthetized rats during thalamic DBS at 7 different frequencies. We related Maximum Change in Reflectance (MCR) from the imaging data to Integrated Evoked Potential (IEP) and change in broadband power of multi-unit (MU) activity, computing Spearman's correlation to determine the strength of these relationships. To determine the source of these effects, we studied the contributions of antidromic versus orthodromic activation in motor cortex perfusion using synaptic blockers. RESULTS: MCR, IEP and change in MU power increased linearly to 60 Hz and saturated at higher frequencies of stimulation. Blocking orthodromic transmission only reduced the DBS-induced change in optical signal by ∼25%, suggesting that activation of corticofugal fibers have a major contribution in thalamic-induced cortical activation. CONCLUSION: DBS-evoked vascular response is related to both evoked field potentials as well as multi-unit activity.

Predicting high-intensity focused ultrasound thalamotomy lesions using 2D magnetic resonance thermometry and 3D Gaussian modeling.

PURPOSE: To develop a method of using two-dimensional (2D) magnetic resonance thermometry, and three-dimensional (3D) Gaussian modeling to predict the volume, shape, and location of 1 day postoperative T1w high-intensity focused ultrasound lesions in medication refractory tremor patients; thereby facilitating a better comprehension of thermal damage thresholds, which can be utilized to reduce adverse events, and improve patient outcome. METHODS: Fifteen patients underwent magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy, which was performed at our center using an InSightec ExAblate 4000 system (Haifa, Israel), and guided by magnetic resonance imaging using a 3 T Discovery 750 (General Electric Healthcare, Waukesha, WI, USA). For treatment monitoring, 2D MR thermometry (temperature sensitivity: -0.00909 ppm/°C, bandwidth: 279 Hz/pixel) was performed in multiple orthogonal planes (sagittal, coronal, and axial) intraoperatively. These images were temporally filtered using a general linear model approach to reduce noise. Temporal volumes of filtered temperature maps with a peak temperature ≥ 47°C were aligned and fitted with a 3D Gaussian to create a canonical heating model. We then fitted the filtered 2D temperature maps with a 3D Gaussian, and used the relationships derived from the 3D heating model to estimate the 3D temperature distribution. These temperature distributions were converted into thermal dose distributions and accumulated across time to create an accumulated thermal dose (ATD) profile. Thresholded ATD profiles were then correlated with manually traced T1-weighted 1 day postoperative lesion volumes across patients, and linear regression slopes were plotted against varying ATD thresholds. Additionally, the Dice-Sørensen coefficient (DSC) was calculated to quantify the volumetric overlap between predicted, and actual lesions. RESULTS: On average, 18.1 (standard deviation (SD): ±4.6, range: 10-29) sonications were performed with an average peak temperature achieved of 62.4°C (SD: ±2.4, range: 58.2-67.7). An ATD threshold of 35.8 CEM43 was found to give a unity linear regression slope; this corresponded to an average DSC of 0.689 (SD: ±0.090, range: 0.476-0.815). CONCLUSIONS: Using multiplanar 2D MR thermometry and 3D Gaussian modeling, we were able to achieve very good (DSC = 0.689) predictions of T1w 1 day postoperative lesion volume, shape and location at an ATD threshold of approximately 36 CEM43. Furthermore, this method has the potential to be used in clinical evaluations to further elucidate the relationship between thermal damage and clinical outcome. Accurate 3D lesion prediction will facilitate improved clinical decision making in future MRgFUS thalamotomies.

Medical Methods Patents in Neuromodulation.

There is a rapidly growing number of patents on methods of modulating brain regions. Despite this trend, and the massive potential of neuromodulation for treating patients, researchers and physicians who use neuromodulation techniques and technologies often have little idea of the significant ways these patents could affect their work. This article describes medical method patents, including a brief history of their development, and analyzes their potential direct and indirect effects on neuromodulation treatment and research efforts. As neuromodulation rapidly matures into a commercial and medical reality it is important to consider these effects in a forward thinking and value driven manner. The paper concludes with recommendations concerning how neuromodulation method patents may be used, or not, depending on the values of the inventor.

Both 50 and 30 Hz continuous theta burst transcranial magnetic stimulation depresses the cerebellum.

The cerebellum is implicated in the pathophysiology of numerous movement disorders, which makes it an attractive target for noninvasive neurostimulation. Continuous theta burst stimulation (cTBS) can induce long lasting plastic changes in human brain; however, the efficacy of different simulation protocols has not been investigated at the cerebellum. Here, we compare a traditional 50-Hz and a modified 30-Hz cTBS protocols at modulating cerebellar activity in healthy subjects. Seventeen healthy adults participated in two testing sessions where they received either 50-Hz (cTBS50) or 30-Hz (cTBS30) cerebellar cTBS. Cerebellar brain inhibition (CBI), a measure of cerebello-thalamocortical pathway strength, and motor evoked potentials (MEP) were measured in the dominant first dorsal interosseous muscle before and after (up to ~ 40 min) cerebellar cTBS. Both cTBS protocols induced cerebellar depression, indicated by significant reductions in CBI (P < 0.001). No differences were found between protocols (cTBS50 and cTBS30) at any time point (P = 0.983). MEP amplitudes were not significantly different following either cTBS protocol (P = 0.130). The findings show cerebellar excitability to be equally depressed by 50-Hz and 30-Hz cTBS in heathy adults and support future work to explore the efficacy of different cerebellar cTBS protocols in movement disorder patients where cerebellar depression could provide therapeutic benefits.

Functional electrical stimulation and spinal cord injury.

Spinal cord injuries (SCI) can disrupt communications between the brain and the body, resulting in loss of control over otherwise intact neuromuscular systems. Functional electrical stimulation (FES) of the central and peripheral nervous system can use these intact neuromuscular systems to provide therapeutic exercise options to allow functional restoration and to manage medical complications following SCI. The use of FES for the restoration of muscular and organ functions may significantly decrease the morbidity and mortality following SCI. Many FES devices are commercially available and should be considered as part of the lifelong rehabilitation care plan for all eligible persons with SCI.

Occipital stimulation for chronic migraine: patient selection and complications.

BACKGROUND: Chronic migraine is a significant cause of disability world-wide and occipital region stimulation (OS) has been proposed to treat it. While participating in an industry-sponsored pilot trial of OS, we aimed to collect data regarding our surgical complications and long term usage of OS in our chronic migraine patients. METHODS: Ten patients (8 female, median age 46.5 years) were enrolled based on criteria established by the sponsoring company, screened in the headache clinic, and followed for a median of 33 months. We did not access data collected by industry for this report and instead collected our own data prospectively, including predominant location of headache, location of paresthesia evoked by OS, and complications. RESULTS: Adverse events included three possible early infections requiring antibiotics but not hardware removal, one late implantable pulse generator erosion requiring removal, one generator malfunction requiring revision, and loss of paresthetic coverage requiring four revisions in four patients. Two patients experienced new symptoms requiring psychiatric intervention. Five patients had no benefit and have been explanted. Of those who remain using their device, the proportion of their pre-operative pain located in the occipital region was 0.62 ± 0.14, whereas in those patients who have been explanted, the proportion was 0.31 ± 0.18 (t = 3.15, p=0.01). CONCLUSIONS: Complication rates with OS are higher than those seen with other stimulation techniques, despite identical hardware and similar surgery. The location of migraine pain did predict outcome, and suggests that only those with primarily occipital region headache are candidates for this therapy.

Designing a thalamic somatosensory neural prosthesis: consistency and persistence of percepts evoked by electrical stimulation.

Intuitive somatosensory feedback is required for fine motor control. Here we explored whether thalamic electrical stimulation could provide the necessary durations and consistency of percepts for a human somatosensory neural prosthetic. Continuous and cycling high-frequency (185 Hz, 0.21 ms pulse duration charge balanced square wave) electrical pulses with the cycling patterns varying between 7% and 67% of duty cycle were applied in five patients with chronically implanted deep brain stimulators. Stimulation produced similar percepts to those elicited immediately after surgery. While consecutive continuous stimuli produced decreasing durations of sensation, the amplitude and type of percept did not change. Cycling stimulation with shorter duty cycles produced more persisting percepts. These features suggest that the thalamus could provide a site for stable and enduring sensations necessary for a long term somatosensory neural prosthesis.

Designing a somatosensory neural prosthesis: percepts evoked by different patterns of thalamic stimulation.

Although major advances have been made in the development of motor prostheses, fine motor control requires intuitive somatosensory feedback. Here we explored whether a thalamic site for a somatosensory neural prosthetic could provide natural somatic sensation to humans. Different patterns of electrical stimulation (obtained from thalamic spike trains) were applied in patients undergoing deep brain stimulation surgery. Changes in pattern produced different sensations, while preserving somatotopic representation. While most percepts were reported as 'unnatural', some stimulations produced more 'natural' sensations than others. However, the additional patterns did not elicit more 'natural' percepts than high-frequency (333 Hz) electrical stimulation. These features suggest that despite some limitations, the thalamus may be a feasible site for a somatosensory neural prosthesis and different stimulation patterns may be useful in its development.

Clinical and experimental aspects of deep brain stimulation.

This presentation will review the effects of deep brain stimulation (DBS) for movement disorders in patients, and the cellular mechanisms that may explain these effects.

Cellular mechanisms preventing sustained activation of cortex during subcortical high-frequency stimulation.

Axonal excitation has been proposed as a key mechanism in therapeutic brain stimulation. In this study we examined how high-frequency stimulation (HFS) of subcortical white matter tracts projecting to motor cortex affects downstream postsynaptic responses in cortical neurons. Whole cell recordings were performed in the primary motor cortex (M1) and ventral thalamus of rat brain slices. In M1, neurons showed only an initial depolarization in response to HFS, after which the membrane potential returned to prestimulation levels. The prolonged suppression of excitation during stimulation was neither associated with GABAergic inhibition nor complete action potential failure in stimulated axons. Instead we found that HFS caused a depression of excitatory synaptic currents in postsynaptic neurons that was specific to the stimulated subcortical input. These data are consistent with the hypothesis that axonal HFS produces a functional deafferentation of postsynaptic targets likely from depletion of neurotransmitter.

Selective attenuation of afferent synaptic transmission as a mechanism of thalamic deep brain stimulation-induced tremor arrest.

Deep brain stimulation (DBS) of the ventrolateral thalamus stops several forms of tremor. Microelectrode recordings in the human thalamus have revealed tremor cells that fire synchronous with electromyographic tremor. The efficacy of DBS likely depends on its ability to modify the activity of these tremor cells either synaptically by stopping afferent tremor signals or by directly altering the intrinsic membrane currents of the neurons. To test these possibilities, whole-cell patch-clamp recordings of ventral thalamic neurons were obtained from rat brain slices. DBS was simulated (sDBS) using extracellular constant current pulse trains (125 Hz, 60-80 micros, 0.25-5 mA, 1-30 s) applied through a bipolar electrode. Using a paired-pulse protocol, we first established that thalamocortical relay neurons receive converging input from multiple independent afferent fibers. Second, although sDBS induced homosynaptic depression of EPSPs along its own pathway, it did not alter the response from a second independent pathway. Third, in contrast to the subthalamic nucleus, sDBS in the thalamus failed to inhibit the rebound potential and the persistent Na+ current but did activate the Ih current. Finally, in eight patients undergoing thalamic DBS surgery for essential tremor, microstimulation was most effective in alleviating tremor when applied in close proximity to recorded tremor cells. However, stimulation could still suppress tremor at distances incapable of directly spreading to recorded tremor cells. These complementary data indicate that DBS may induce a "functional deafferentation" of afferent axons to thalamic tremor cells, thereby preventing tremor signal propagation in humans.

The Canadian multicenter trial of pallidal deep brain stimulation for cervical dystonia: preliminary results in three patients.

OBJECT: Deep brain stimulation (DBS) of the globus pallidus internus (GPi) is beneficial for generalized dystonia and has been proposed as a treatment for cervical dystonia. The Canadian Stereotactic/Functional and Movement Disorders Groups designed a pilot project to investigate the following hypothesis: that bilateral DBS of the GPi will reduce the severity of cervical dystonia at 1 year of follow up, as scored in a blinded fashion by two neurologists using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS). Secondary outcome measures included pain and disability subscores of the TWSTRS, Short Form-36 quality of life index, and the Beck Depression Inventory. METHODS: Three patients have undergone surgery in Calgary with a follow-up duration of 7.4 +/- 5.9 months (mean +/- standard deviation). One patient underwent inadvertent ineffective stimulation for the first 3 months and did not experience a benefit until DBS programming was corrected. All three patients had rapid response to stimulation, with the muscles relaxing immediately and abnormal movements improving within days. Total TWSTRS scores improved by 79%, and severity subscores improved significantly, from 15.7 +/- 2.1 to 7.7 +/- 2.9 (paired t-test, p = 0.02). Pain and disability subscores improved from 25.5 +/- 4.1 to 3.3 +/- 3.1 (paired t-test, p = 0.002) and from 13.3 +/- 4.9 to 3.3 +/- 4.2 (paired t-test, p = 0.06), respectively. CONCLUSIONS: Although it is too early to reach broad conclusions, this report of preliminary results confirms the efficacy of DBS of the GPi for cervical dystonia.

Mechanisms of deep brain stimulation: an intracellular study in rat thalamus.

High-frequency deep brain stimulation (DBS) in the thalamus alleviates most kinds of tremor, yet its mechanism of action is unknown. Studies in subthalamic nucleus and other brain sites have emphasized non-synaptic factors. To explore the mechanism underlying thalamic DBS, we simulated DBS in vitro by applying high-frequency (125 Hz) electrical stimulation directly into the sensorimotor thalamus of adult rat brain slices. Intracellular recordings revealed two distinct types of membrane responses, both of which were initiated with a depolarization and rapid spike firing. However, type 1 responses repolarized quickly and returned to quiescent baseline during simulated DBS whereas type 2 responses maintained the level of membrane depolarization, with or without spike firing. Individual thalamic neurones exhibited either type 1 or type 2 response but not both. In all neurones tested, simulated DBS-evoked membrane depolarization was reversibly eliminated by tetrodotoxin, glutamate receptor antagonists, and the Ca(2+) channel antagonist Cd(2+). Simulated DBS also increased the excitability of thalamic cells in the presence of glutamate receptor blockade, although this non-synaptic effect induced no spontaneous firing such as that found in subthalamic nucleus neurones. Our data suggest that high-frequency stimulation when applied in the ventral thalamus can rapidly disrupt local synaptic function and neuronal firing thereby leading to a 'functional deafferentation' and/or 'functional inactivation'. These mechanisms, driven primarily by synaptic activation, help to explain the paradox that lesions, muscimol and DBS in thalamus all effectively stop tremor.

Is the target for thalamic deep brain stimulation the same as for thalamotomy?

Deep brain stimulation (DBS) has virtually replaced thalamotomy for the treatment of essential tremor. It is thought that the site for DBS is the same as the optimal lesion site; however, this match has not been investigated previously. We sought to determine whether the location of thalamic DBS matched the site at which thalamotomy would be performed. Eleven patients who had detailed microelectrode recording and stimulation for placement of DBS electrodes and subsequent successful tremor control were analysed. An experienced surgeon, blinded to outcome and final electrode position, selected the ideal thalamotomy site based on the reconstructed maps obtained intraoperatively. When the site of long-term clinically used DBS and theoretical thalamotomy location was calculated in three-dimensional space and compared for each of the x, y, and z axes in stereotactic space, there was no significant difference in the mediolateral location of DBS and theoretical lesion site. There was also no difference between the theoretical lesion site and the placement of the tip of the electrode; however, the active electrodes used for chronic stimulation were significantly more anterior (P = 0.005) and dorsal (P = 0.034) to the ideal thalamotomy target. This mismatch may reflect the compromise required between adverse and beneficial effects with chronic stimulation, but it also suggests different mechanisms of effect of DBS and thalamotomy.

Neural substrates of microstimulation-evoked tingling: a chronaxie study in human somatosensory thalamus.

Intra-operative micro-electrode stimulation of sensorimotor thalamus produces paraesthesia or tingling in various body regions and is used to map somatotopy prior to implantation of deep brain-stimulating electrodes in awake patients. The neural elements affected by such microstimulation are unknown. Using paraesthesia as the behavioural-physiological response threshold, we measured chronaxie times for microstimuli applied to both somatosensory thalamic nuclei (cellular region) and its axonal afferents, the medial lemniscus. White matter chronaxie times were relatively unimodal, whereas two different clusters of chronaxie times were identified in grey matter: one corresponding to that of the medial lemniscus and the other about five times longer and compatible with that obtained from cell somata. Therefore, excitations of local axons and/or cell bodies can both contribute to the paraesthesia evoked during intra-operative thalamic mapping.