Distinct roles of dorsal and ventral subthalamic neurons in action selection and cancellation

The subthalamic nucleus (STN) supports action selection by inhibiting all motor programs except the desired one. Recent evidence suggests that STN can also cancel an already selected action when goals change, a key aspect of cognitive control. However, there is little neurophysiological evidence for dissociation between selecting and cancelling actions in the human STN. We recorded single neurons in the STN of humans performing a stop-signal task. Movement-related neurons suppressed their activity during successful stopping, whereas stop-signal neurons activated at low-latencies near the stop-signal reaction time. In contrast, STN and motor-cortical beta-bursting occurred only later in the stopping process. Task-related neuronal properties varied by recording location from dorsolateral movement to ventromedial stop-signal tuning. Therefore, action selection and cancellation coexist in STN but are anatomically segregated. These results show that human ventromedial STN neurons carry fast stop-related signals suitable for implementing cognitive control

Steering the Volume of Tissue Activated With a Directional Deep Brain Stimulation Lead in the Globus Pallidus Pars Interna: A Modeling Study With Heterogeneous Tissue Properties

Objective: To study the effect of directional deep brain stimulation (DBS) electrode configuration and vertical electrode spacing on the volume of tissue activated (VTA) in the globus pallidus, pars interna (GPi). Background: Directional DBS leads may allow clinicians to precisely direct current fields to different functional networks within traditionally targeted brain areas. Modeling the shape and size of the VTA for various monopolar or bipolar configurations can inform clinical programming strategies for GPi DBS. However, many computational models of VTA are limited by assuming tissue homogeneity. Methods: We generated a multimodal image-based detailed anatomical (MIDA) computational model with a directional DBS lead (1.5 mm or 0.5 mm vertical electrode spacing) placed with segmented contact 2 at the ventral posterolateral “sensorimotor” region of the GPi. The effect of tissue heterogeneity was examined by replacing the MIDA tissues with a homogeneous tissue of conductance 0.3 S/m. DBS pulses (amplitude: 1 mA, pulse width: 60 μs, frequency: 130 Hz) were used to produce VTAs. The following DBS contact configurations were tested: single-segment monopole (2B-/Case+), two-segment monopole (2A-/2B-/Case+ and 2B-/3B-/Case+), ring monopole (2A-/2B-/2C-/Case+), one-cathode three-anode bipole (2B-/3A+/3B+/3C+), three-cathode three-anode bipole (2A-/2B-/2C-/3A+/3B+/3C+). Additionally, certain vertical configurations were repeated with 2 mA current amplitude. Results: Using a heterogeneous tissue model affected both the size and shape of the VTA in GPi. Electrodes with both 0.5 mm and 1.5 mm vertical spacing (1 mA) modeling showed that the single segment monopolar VTA was entirely contained within the GPi when the active electrode is placed at the posterolateral “sensorimotor” GPi. Two segments in a same ring and ring settings, however, produced VTAs outside of the GPi border that spread into adjacent white matter pathways, e.g., optic tract and internal capsule. Both stacked monopolar settings and vertical bipolar settings allowed activation of structures dorsal to the GPi in addition to the GPi. Modeling of the stacked monopolar settings with the DBS lead with 0.5 mm vertical electrode spacing further restricted VTAs within the GPi, but the VTA volumes were smaller compared to the equivalent settings of 1.5 mm spacing

A new neurosurgical tool incorporating differential geometry and cellular automata techniques

Using optical coherence imaging, it is possible to visualize seizure progression intraoperatively. However, it is difficult to pinpoint an exact epileptic focus. This is crucial in attempts to minimize the amount of resection necessary during surgical therapeutic interventions for epilepsy and is typically done approximately from visual inspection of optical coherence imaging stills. In this paper, we create an algorithm with the potential to pinpoint the source of a seizure from an optical coherence imaging still. To accomplish this, a grid is overlaid on optical coherence imaging stills. This then serves as a grid for a two-dimensional cellular automation. Each cell is associated with a Riemannian curvature tensor representing the curvature of the brain's surface in all directions for a cell. Cells which overlay portions of the image which show neurons that are firing are considered "depolarized"

Parietal neural prosthetic control of a computer cursor in a graphical-user-interface task

Objective. To date, the majority of Brain–Machine Interfaces have been used to perform simple tasks with sequences of individual targets in otherwise blank environments. In this study we developed a more practical and clinically relevant task that approximated modern computers and graphical user interfaces (GUIs). This task could be problematic given the known sensitivity of areas typically used for BMIs to visual stimuli, eye movements, decision-making, and attentional control. Consequently, we sought to assess the effect of a complex, GUI-like task on the quality of neural decoding. Approach. A male rhesus macaque monkey was implanted with two 96-channel electrode arrays in area 5d of the superior parietal lobule. The animal was trained to perform a GUI-like 'Face in a Crowd' task on a computer screen that required selecting one cued, icon-like, face image from a group of alternatives (the 'Crowd') using a neurally controlled cursor. We assessed whether the crowd affected decodes of intended cursor movements by comparing it to a 'Crowd Off' condition in which only the matching target appeared without alternatives. We also examined if training a neural decoder with the Crowd On rather than Off had any effect on subsequent decode quality. Main results. Despite the additional demands of working with the Crowd On, the animal was able to robustly perform the task under Brain Control. The presence of the crowd did not itself affect decode quality. Training the decoder with the Crowd On relative to Off had no negative influence on subsequent decoding performance. Additionally, the subject was able to gaze around freely without influencing cursor position. Significance. Our results demonstrate that area 5d recordings can be used for decoding in a complex, GUI-like task with free gaze. Thus, this area is a promising source of signals for neural prosthetics that utilize computing devices with GUI interfaces, e.g. personal computers, mobile devices, and tablet computers

A shared neural substrate for action verbs and observed actions in human posterior parietal cortex

High-level sensory and motor cortical areas are activated when processing the meaning of language, but it is unknown whether, and how, words share a neural substrate with corresponding sensorimotor representations. We recorded from single neurons in human posterior parietal cortex (PPC) while participants viewed action verbs and corresponding action videos from multiple views. We find that PPC neurons exhibit a common neural substrate for action verbs and observed actions. Further, videos were encoded with mixtures of invariant and idiosyncratic responses across views. Action verbs elicited selective responses from a fraction of these invariant and idiosyncratic neurons, without preference, thus associating with a statistical sampling of the diverse sensory representations related to the corresponding action concept. Controls indicated that the results are not the product of visual imagery or arbitrary learned associations. Our results suggest that language may activate the consolidated visual experience of the reader

Management of Low-Grade Glioma

The optimal management of patients with low-grade glioma (LGG) is controversial. The controversy largely stems from the lack of well-designed clinical trials with adequate follow-up to account for the relatively long progression-free survival and overall survival of patients with LGG. Nonetheless, the literature increasingly suggests that expectant management is no longer optimal. Rather, there is mounting evidence supporting active management including consideration of surgical resection, radiotherapy, chemotherapy, molecular and histopathologic characterization, and use of modern imaging techniques for monitoring and prognostication. In particular, there is growing evidence favoring extensive surgical resection and increasing interest in the role of chemotherapy (especially temozolomide) in the management of these tumors. In this review, we critically analyze emerging trends in the literature with respect to management of LGG, with particular emphasis on reports published during the past year

Intrinsic Variable Learning for Brain-Machine Interface Control by Human Anterior Intraparietal Cortex

Although animal studies provided significant insights in understanding the neural basis of learning and adaptation, they often cannot dissociate between different learning mechanisms due to the lack of verbal communication. To overcome this limitation, we examined the mechanisms of learning and its limits in a human intracortical brain-machine interface (BMI) paradigm. A tetraplegic participant controlled a 2D computer cursor by modulating single-neuron activity in the anterior intraparietal area (AIP). By perturbing the neuron-to-movement mapping, the participant learned to modulate the activity of the recorded neurons to solve the perturbations by adopting a target re-aiming strategy. However, when no cognitive strategies were adequate to produce correct responses, AIP failed to adapt to perturbations. These findings suggest that learning is constrained by the pre-existing neuronal structure, although it is possible that AIP needs more training time to learn to generate novel activity patterns when cognitive re-adaptation fails to solve the perturbations

Intrinsic Variable Learning for Brain-Machine Interface Control by Human Anterior Intraparietal Cortex

Although animal studies provided significant insights in understanding the neural basis of learning and adaptation, they often cannot dissociate between different learning mechanisms due to the lack of verbal communication. To overcome this limitation, we examined the mechanisms of learning and its limits in a human intracortical brain-machine interface (BMI) paradigm. A tetraplegic participant controlled a 2D computer cursor by modulating single-neuron activity in the anterior intraparietal area (AIP). By perturbing the neuron-to-movement mapping, the participant learned to modulate the activity of the recorded neurons to solve the perturbations by adopting a target re-aiming strategy. However, when no cognitive strategies were adequate to produce correct responses, AIP failed to adapt to perturbations. These findings suggest that learning is constrained by the pre-existing neuronal structure, although it is possible that AIP needs more training time to learn to generate novel activity patterns when cognitive re-adaptation fails to solve the perturbations

Dose dense 1 week on/1 week off temozolomide in recurrent glioma: a retrospective study

Alternative temozolomide regimens have been proposed to overcome O6-methylguanine-DNA methyltransferase mediated resistance. We investigated the efficacy and tolerability of 1 week on/1 week off temozolomide (ddTMZ) regimen in a cohort of patients treated with ddTMZ between 2005 and 2011 for the progression of a glioblastoma during or after chemo-radiation with temozolomide or a recurrence of another type of glioma after radiotherapy and at least one line of chemotherapy. Patients received ddTMZ at 100–150 mg/m2/d (days 1–7 and 15–21 in cycles of 28-days). All patients had a contrast enhancing lesion on MRI and the response was assessed by MRI using the RANO criteria; complete and partial responses were considered objective responses. Fifty-three patients were included. The median number of cycles of ddTMZ was 4 (range 1–12). Eight patients discontinued chemotherapy because of toxicity. Two of 24 patients with a progressive glioblastoma had an objective response; progression free survival at 6 months (PFS-6) in glioblastoma was 29%. Three of the 16 patients with a recurrent WHO grade 2 or 3 astrocytoma or oligodendroglioma or oligo-astrocytoma without combined 1p and 19q loss had an objective response and PFS-6 in these patients was 38%. Four out of the 12 evaluable patients with a recurrent WHO grade 2 or 3 oligodendroglioma or oligo-astrocytoma with combined 1p and 19q loss had an objective response; PFS-6 in these patients was 62%. This study indicates that ddTMZ is safe and effective in recurrent glioma, despite previous temozolomide and/or nitrosourea chemotherapy. Our data do not suggest superior efficacy of this schedule as compared to the standard day 1–5 every 4 weeks schedule